BORRELIOOSI/ALZHEIMER

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1. Alzheimerin tautia sairastavilta on löydetty borreliabakteereita esim. aivokudoksista, pimeäkenttämikroskooppisella tutkimuksella, verestä ja selkäydinnesteestä (useita tutkimuksia):


1. Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.
Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 673-81.
PMID: 15665404 [PubMed - indexed for MEDLINE]

2: Kuntzer T, Bogousslavsky J, Miklossy J, Steck AJ, Janzer R, Regli F.
Borrelia rhombencephalomyelopathy.
Arch Neurol. 1991 Aug;48(8 ):832-6.
PMID: 1898257 [PubMed - indexed for MEDLINE]

3: Miklossy J, Kuntzer T, Bogousslavsky J, Regli F, Janzer RC. Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis.
Acta Neuropathol (Berl). 1990;80(5):568-72.
PMID: 2251916 [PubMed - indexed for MEDLINE]

4. Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer's disease.

Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H.
University Institute of Pathology, Division of Neuropathology, Lausanne, Switzerland.Neuroreport. 1994 Jun 2;5(10):1201-4.

Recently it was reported that, at autopsy, in neuropathologically confirmed cases of Alzheimer's disease spirochaetes were found in blood and cerebrospinal fluid using dark-field microscopy. Moreover, the spirochaetes were isolated and cultured from brain tissue. We now show, using scanning electron microscopy and atomic force microscopy that the helically shaped microorganisms isolated and cultured from the Alzheimer brains possess axial filaments. This indicates that these microorganisms taxonomically indeed belong to the order Spirochaetales. A morphometric analysis reinforces this notion.

PMID: 7919164 [PubMed - indexed for MEDLINE]


2. Alzheimerin taudin ja bakteerien yhteys saa vahvistusta uusista tutkimuksista. Tautia sairastavilta on nyt löydetty kohonneita arvoja myös helikobakteeria vastaan.

http://www.ncbi.nlm.nih.gov/entrez/quer ... &DB=pubmed

Med Hypotheses. 2007;68(2):378-88. Epub 2006 Sep 18.

Alzheimer's disease and Helicobacter pylori infection: Defective immune regulation and apoptosis as proposed common links.

* Kountouras J,
* Gavalas E,
* Zavos C,
* Stergiopoulos C,
* Chatzopoulos D,
* Kapetanakis N,
* Gisakis D.

Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.

Although degenerative diseases of the central nervous system, including Alzheimer's disease (AD), have an increasingly high impact on aged population their association with Helicobacter pylori (H. pylori) infection has not as yet been thoroughly researched. Current H. pylori infection appears to induce irregular humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with components of nerves, thereby contributing and possibly perpetuating the apoptotic neural tissue damage observed in neurodegenerative diseases including AD.

An association between AD and H. pylori infection has been recently addressed by two studies. A higher seropositivity for anti-H. pylori immunoglobulin G antibodies in 30 patients with AD than in 30 age-matched controls was reported in one study; this serological test, however, has limitations because it does not discriminate between current and old infections. In the other study, by introducing the histological method (the actual gold standard) for diagnosis of H. pylori infection, we reported a higher prevalence of H. pylori infection in 50 AD patients than in 30 anemic controls. This pathogen may influence the pathophysiology of AD by promoting platelet and platelet-leukocyte aggregation; releasing various pro-inflammatory and vasoactive substances; developing cross-mimicry with host antigens; producing reactive oxygen metabolites and circulating lipid peroxides; influencing the apoptotic process; and increasing, through induction of atrophic gastritis, homocysteine, which contributes to vascular disorders implicated in endothelial damage and neurodegeneration.

PMID: 16979298 [PubMed - in process]


3. Tutkimuksien mukaan on yleisesti tiedossa, että systeemiset infektiot laukaisevat esim. astma-, reuma-, MS- oireet (esim. ylempien hengitysteiden infektiot). Tässä tutkimuksessa etsitään tukea olettamukselle että kroonisissa neurologisissa sairauksissa kuten Alzheimerin taudissa systeemiset infektiot voivat aiheuttaa oireiden pahenemisen ja sairauden etenemisen.

Nature Reviews Immunology 7, 161-167 (February 2007) | doi:10.1038/nri2015

Systemic infections and inflammation affect chronic neurodegeneration

V. Hugh Perry1, Colm Cunningham1 and Clive Holmes1

Abstract

It is well known that systemic infections cause flare-ups of disease in individuals with asthma and rheumatoid arthritis, and that relapses in multiple sclerosis can often be associated with upper respiratory-tract infections. Here we review evidence to support our hypothesis that in chronic neurodegenerative diseases such as Alzheimer's disease, with an ongoing innate immune response in the brain, systemic infections and inflammation can cause acute exacerbations of symptoms and drive the progression of neurodegeneration.

Author affiliations

1. V. Hugh Perry, Colm Cunningham and Clive Holmes are at the Southampton Neuroscience Group, School of Biological Sciences and School of Medicine, University of Southampton, Southampton SO16 7PX, UK.

Correspondence to: V. Hugh Perry1 Email: vhp@soton.ac.uk

http://www.nature.com/nri/journal/v7/n2/index.html

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Borreliabakteeri hakeutuu esim. keskushermostoon ja saattaa olla yhteydessä Alzheimerin tautiin:


Journal of Alzheimer?s Disease Vol 6 No. 6 Pages 639-649 Dec. 2004

Judith Miklossy, Kamel Khalili, Lise Gern, Rebecca L. Ericson, Pushpa Darekar, Lorie Bolle, Jean Hurlimann, Bruce J. Paster


Borrelia burgdorferi persists in the brain in chronic Lyme neuroborreliosis and may be associated with Alzheimer?s disease

Abstract: The cause, or causes, of the vast majority of Alzheimer?s disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases.

The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.

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Artikkelin mukaan Alzheimerin taudille tyypilliset aivomuutokset (plakit) saattavat johtua kystamuotoisista borreliabakteereista.

Med Hypotheses. 2006;67(3):592-600. Epub 2006 May 3.

Plaques of Alzheimer's disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete.


MacDonald AB.
St. Catherine of Siena Medical Center, Department of Pathology, 50 Rte 25 A, Smithtown, NY 11787, USA. inmacdonald@yahoo.com

Here is hypothesized a truly revolutionary notion that rounded cystic forms of Borrelia burgdorferi are the root cause of the rounded structures called plaques in the Alzheimer brain. Rounded "plaques' in high density in brain tissue are emblematic of Alzheimer's disease (AD). Plaques may be conceptualized as rounded "pock mark-like" areas of brain tissue injury. In this century, in brain tissue of AD, plaques are Amyloid Plaques according to the most up to date textbooks. In the last century, however, Dr. Alois Alzheimer did not require amyloid as the pathogenesis for either the disease or for the origin of its plaques. Surely, amyloid is an event in AD, but it may not be the primal cause of AD. Indeed in plaques, amyloid is regularly represented by the "congophilic core" structure which is so named because the waxy amyloid material binds the congo red stain and is congophilic. However an accepted subset of plaques in AD is devoid of a congophilic amyloid core region (these plaques "cotton wool" type plaques, lack a central congophilic core structure). Furthermore, there is "plaque diversity" in Alzheimer's; small, medium and large plaques parallel variable cystic diameters for Borrelia burgdorferi. Perturbations of AD plaque structure (i.e. young plaques devoid of a central core and older plaques with or without a central core structure) offer room for an alternate pathway for explanation of ontogeny of the plaque structures. If amyloid is not required to initiate all of the possible plaques in Alzheimer's, is it possible that amyloid just a by product of a more fundamental primal path to dementia? If a byproduct status is assigned to amyloid in the realm of plaque formation, then is amyloid also an epiphenomenon rather than a primary pathogenesis for Alzheimer's disease. In the "anatomy is destiny" model, cysts of borrelia are always round. Why then not accept roundness as a fundamental "structure determines function" argument for the answer to the mystery of why Alzheimer plaques are always round? Parataxis causality, a concept borrowed from philosophy, is the error that comes from linking two events, which occur contemporaneously or in close proximity to one another with a cause and effect relationship. Parataxis tells us that what appears to be cause and effect in the couplet "amyloid plaque" merely by a proximity relationship may be "spurious causality" which is a cognitive dead end.

PMID: 16675154 [PubMed - indexed for MEDLINE]

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1. "Tri MacDonaldin huolellisesti dokumentoidussa tapaustutkimuksessa esitetään borrelioosia sairastanut mies jonka aivoista löydettiin kuoleman jälkeen spirokeettojen DNA:ta. Mies kuoli Alzheimerin taudin oireisiin. MacDonaldin uusimman havainnon mukaan biofilmit suojelevat ja kätkevät borreliabakteeriyhdyskuntia esim. antibiooteilta.

Hänen mukaansa spirokeetat voivat esiintyä ilman selkeää spirokeettamuotoa ja kuitenkin aiheuttaa sairauden. Epäsuotuisissa olosuhteissa spirokeettojen selvitymiskeinona on muuntua erilaisiin muotoihin ja yhdistyä yhdyskunniksi."

http://www.prweb.com/releases/2008/04/prweb852784.htm

2. Artikkelin mukaan Alzheimerin taudin syynä voivat olla useat bakteerit ja/tai virukset.

Suom.huom. Esim. borreliabakteeri, mykoplasma ja keuhkoklamydia ovat taudin mahdollisia aiheuttajia. Valitettavasti borrelioosiin sairastuneilta on löydetty toistuvasti esim. kaikkia edellämainittuja bakteereita.

Medical Doctor Discusses Link Between Lyme Disease and Alzheimer's on 'Interviews with Experts' Series
Alan MacDonald, MD, discusses the connection between Lyme Disease and Alzheimer's on the 'Interviews with Experts' series. Lyme is sometimes misdiagnosed as Alzheimer's disease, as the two share symptoms. Research also yields discovery of biofilms, a form of defense taken by the Lyme bacteria. The interview series provides medical experts a platform for talking directly to people affected by Lyme about diagnosis, symptoms and treatment of Lyme disease.

Asheville, NC (PRWEB) April 14, 2008 -- Alan MacDonald, MD, talks about his research into the link between Lyme disease and Alzheimer's in the audio series 'Interviews with Experts,' on the Lyme Disease Research Database. Lyme is sometimes misdiagnosed as Alzheimer's, as the two diseases share common symptoms. Recent research also includes the discovery of biofilms, another of the stealth forms taken by the Lyme bacteria. The interview series provides medical experts an online platform for reaching people affected by Lyme.

Read the interview transcript.
http://www.lyme-disease-research-databa ... ption.html

Dr. MacDonald discusses his research in a well-documented case study at Stony Brook Hospital, which showed spirochetal DNA in the brain tissue of a man who was diagnosed with Lyme and eventually succumbed to Alzheimer's disease, therefore "connecting the link between Lyme disease and Alzheimer's in some patients," he says. He also describes the recent discovery of biofilms, which hide and protect colonies of spirochetes. Biofilms are one of the various stealth forms taken by Borrelia burgdorferi bacteria to evade antibiotics.

"It helps to understand that a group of spirochetes with the DNA and the potential to cause disease can exist without having a single spiral form at all, but they have other diverse forms as they unite into a colony to survive under adverse conditions," says Dr. MacDonald, who will present a summary of his research into biofilms at the 3rd Annual Lyme Disease Symposium at New Haven University, Connecticut on May 17.

The 'Interviews with Experts' series, available online at the Lyme Disease Research Database, provides health experts with a platform for reaching patients and others affected by the disease. In other interviews, renowned physician and medical researcher Dr. Lee Cowden discusses his Lyme protocol, and master herbalist Stephen Harrod Buhner talks about the politics of Lyme and his book, Healing Lyme: Natural Healing and Prevention of Borreliosis and its Coinfections.

Learn more about the Lyme expert audio interview series-
http://www.lyme-disease-research-databa ... eries.html

For additional information on the Lyme Disease Research Database, visit www.lyme-disease-research-database.com. Access to the cutting edge news from experts on Lyme disease is available immediately.

Learn more about Lym disease symptoms.
http://www.lyme-disease-research-databa ... ptoms.html

Private health and wellness advocates have been gathering information on conventional and integrative approaches to heal from Lyme disease since 2005.

Other Releases by this Member
Lyme Disease Researchers Launch Part Two of Audio Interview Series with Lyme Experts 2008-03-10
Clinical Study Tests Herbal Protocol for Effectiveness in Treatment of Chronic Lyme Disease; Successful Protocol Interests Doctors and Lyme Patients Seeking Alternatives to Antibiotics 2007-03-19
Lyme Experts Discuss Alternatives to Antibiotics for Treatment of Lyme Disease on Interview Series 2006-12-18
Healthy Survivor of Lyme Disease Discusses Successful Therapy on Lyme Research Interview Series 2006-11-09
Naturopath Discusses the Role of Stress in Lyme Disease in Interview Series 2006-09-25


The Emerging Role Of Infection In Alzheimer's Disease

ScienceDaily (May 22, 2008) ? A number of chronic diseases are in fact caused by one or more infectious agents. For example, stomach ulcers are caused by Helicobacter pylori, chronic lung disease in newborns and chronic asthma in adults are both caused by Mycoplasmas and Chlamydia pneumonia, while some other pathogens have been associated with atherosclerosis. The realization that pathogens can produce slowly progressive chronic diseases has opened new lines of research into Alzheimer's disease.
In a special issue of the Journal of Alzheimer's Disease published May 2008, guest editors Judith Miklossy, from The University of British Columbia, and Ralph N. Martins, from Edith Cowan University and Hollywood Private Hospital, Perth, Western Australia, and a group of experts explore this exciting topic.

Alzheimer's disease (AD), the most frequent cause of dementia, is a form of amyloidosis. It has been known for a century that dementia, brain atrophy and amyloidosis can be caused by chronic bacterial infections, namely by Treponema pallidum in the atrophic form of general paresis in syphilis. Bacteria and viruses are powerful stimulators of inflammation. It was suggested by Alois Alzheimer and his colleagues a century ago that microorganisms may be contributors in the generation of senile plaques in AD.

The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells may cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the organism can persist in the infected tissues and cause chronic inflammation and amyloid deposition. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors and nutrition are critical determinants of disease expression as well.

In this special issue a series of reviews draws attention to both historic and recent observations related to this emerging field of AD research. The first review shows the importance of chronic inflammation in AD, followed by three articles presenting evidence on the involvement of spirochetes, Chlamydia pneumoniae and Herpes simplex virus type 1 in AD. These are followed by a review of amyloid proteins, which occur in many cellular forms in Eukaryotes and Prokaryotes.

The link between several viral and bacterial infections and the most significant genetic factor for AD, APOE å4, is discussed in the next review. The link between excessive or misplaced iron and a variety of neurodegenerative diseases and infection is reviewed in the final article.

According to Miklossy and Martins, "The historic and new observations reviewed in this special issue clearly show that high priority should be given for further research in this field as it may have major implications for public health, treatment, and prevention as adequate anti-bacterial and anti-viral drugs are available. Treatment of a bacterial infection and associated viral infection may result in regression and, if started early, prevention of disease. The impact on reducing healthcare costs would be substantial."

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Tri Alan McDonald on keskittynyt tutkimaan borreliabakteerin ja Alzheimerin taudin välistä yhteyttä tutkimalla Alzheimerin tautia sairastavien selkäydin-ja kudosnäytteitä. Borreliabakteerilla on useita erilaisia selviytymismenetelmiä esim. kystamuoto ja biofilmit.

Tutkimustuloksista on lisätietoa sivulla http://www.molecularalzheimer.org.

http://www.lyme-disease-research-databa ... ption.html

Alan MacDonald, M.D., is a pathologist affiliated with St. Catherine of Siena Medical Center in Smithtown, New York. His current research is concentrated on developing what he refers to as a new biology for Lyme disease, including the use of special DNA probes to detect Borrelia DNA in spinal fluid and in tissue sections from Alzheimer autopsy tissues.

Through his research, and with the help of other leading researchers in the field of molecular and cellular biology, Dr. MacDonald is pioneering a broader understanding about the behavior of Borrelia burgdorferi, the bacteria that causes Lyme disease. He has appeared as an invited lecturer at Lyme symposia, including the ILADS National Scientific Meetings and Columbia University/Lyme Disease Association conferences in Philadelphia, PA, where he presents the findings from his explorations into the connection between Borrelia spirochetal infection and Alzheimer's disease.


Dr. MacDonald initially began working with the model of Lyme disease and pregnancy, and had developed techniques to identify the spirochete in tissue, from either biopsy or autopsy tissues, and applied those techniques to the study of the fetuses. He was then able to transition from pathology to studies of brain tissue. His interest in Alzheimer's disease and Lyme began when attending a Lyme disease conference in Vienna, Austria. The speakers were describing Lyme disease as having three stages: primary, secondary and tertiary. Since those terms are also used to describe syphilis, it occurred to him that if Lyme disease had a tertiary, late-stage form, perhaps the late manifestation could be dementia. Like syphilis, which also had late stage dementia, Lyme disease may reoccur thirty or forty years after infection. He hypothesized that if there is a dementia occurring in late-stage Lyme, it might be an Alzheimer's-like illness, a late manifestation of bacterial infection in the brain.


Dr. Alan MacDonald: "Using the syphilis model, I began to study some autopsied brains, and found that I was able to identify spirochetes in autopsied brain tissue in the hippocampus, which is one of the areas that Alzheimer's disease tends to target in every patient. I was able to grow spirochetes from autopsied Alzheimer's brain tissue, and stain the spirochetes with special monochromal antibodies, through the techniques I learned and developed through the study of stillborn babies with Lyme disease. And those two positive results made me think even more strongly that some Alzheimer's might be like syphilis, a late manifestation of the bacterial infection in the brain, not to say that all Alzheimer's disease is related to Lyme disease, but some.

Over the years, I had carried that theme a little further, and done some more work, and thought more about it. I tried to establish ways that we could make connection between the pathology findings of Alzheimer's disease and a spirochetal infection in the brain, which moves from the hippocampus to the higher memory centers in the brain. I had some success with that line of reasoning in 2004, 2005."

Dr. MacDonald delivered a summary of his research findings at a Philadelphia, PA meeting of the LDA Lyme Disease Association and ILADS. That lecture and accompanying images is accessible through Dr. MacDonald's website: http://www.molecularalzheimer.org.

"So, using the microscope, and using the model of syphilis I was able to develop some ideas and test the hypothesis and get some encouraging, positive results," he says.

Case Study: Paul Christensen

One of Dr. MacDonald's most exciting research results comes from a uniquely well-documented case of one man who passed away from Alzheimer's disease, Paul Christensen, and was autopsied at Stony Brook in Long Island. A firefighter, Christensen was diagnosed with Lyme disease when the Borrelia bacteria was found in his spinal fluid. He was treated for a short time by doctors at Stony Brook University Hospital and then released. However, his diagnosis of Lyme was followed by an eight year period of mental deterioration, and he ultimately died from Alzheimer's disease.

Christensen's wife, in an effort to support and encourage Dr. MacDonald to help educate the medical community about the connection between Lyme and Alzheimer's disease, contacted him and allowed him access to study Christensen's brain tissue for clues about this connection. Dr. MacDonald was "able to show that those areas of Alzheimer-type injury in the brain also lit up for spirochetal DNA, with special florescent dye attached to the DNA probe."

Through his work in the thoroughly researched, well-evaluated Christensen case, which he confirms has been one of the most exciting cases he has worked on, Dr. MacDonald learned that using DNA probes allowed him another point of reference in order to show the spirochetal DNA in the brain tissue, and therefore, "make the connection between Lyme disease and Alzheimer's in some patients," he says.

The Canadian Lyme foundation has a number of links to my work, and also has published the case of Paul Christensen on their website: http://www.canlyme.com.

How is Alzheimer's disease treated?

"Alzheimer's disease is treated with comfort care. They give patients support, but don't use any antibiotic treatment. They give treatment to prolong the survival of some of the neurotransmitters of the brain, such as Aricept. These medicines help to prolong periods where patients can have some functional independence. But it does not slow the disease down, or shorten the disease."

How commonly known is your research, and the link between Alzheimer's and Lyme disease?

"The people who attended the symposia that were held in Philadelphia and those who know about ILADS would probably know about my work. I don't know if everybody who sees patients know about my work. It's probably more likely that people in the northeast will know about it. You can do a Google search for Alzheimer's and Borrelia, you'll find my papers on the Internet. You'll also find papers from people who dispute the connection as well, but it's in the public domain for people to look at."

What is the spirochete and what does it do?

"People think of the spirochete as the spiral form, corkscrew shaped form, and that is what you'll read about if you look in a biology or medical textbook. You'll see that spirochetes are different from other bacteria because they are long and curly. They expect to see that when they look in tissue.

Unfortunately, spirochetes have more diverse forms than just the corkscrew, or spiral form. One of the functions of my website is to call attention to the other forms that exist that are just as legitimate as the spiral form. If you took the spiral and you reduce it to dashes and dots, those little dots contain DNA, and those are smaller units of the spirochete. There are also rounded balloon-like form called the cystic form. Spirochetes in certain circumstances will round up and make a round balloon-like structure, which has its DNA, and that is a second form. And then there are a number of very easily distorted forms called L-forms, which are sort of like soap bubbles that can stretch out and contain various boundaries, and are not as easy to identify as spirochetes, but they are also a part of the mixture of forms that the spirochete can have.

One of the functions of my website is to call attention to the fact that not only is this true for the Borrelia spirochete, but it's true for the syphilis spirochete, its related morphology, or shape changes are common to the two.

If you're looking for evidence of an infection in tissue you want to see the bug. And if you're looking for the bug and you only look for spiral forms, you may miss the other forms, forms that are granular or rounded cyst forms or L-forms."

Research yields discovery of Borrelia biofilms

"One of the most exciting things we've come across in the last six months is the idea that, in addition to all these forms, there are groupings of spirochetes, or colonies, that are biofilms. Biofilms are one of the things that bacteria use to promote their survival in adverse conditions.

We've shown, in our preliminary work, Dr. Eva Sapi and I, that Borrelia biofilms are part of the biology of Borrelia. And that these biofilms are ways or strategies for spirochetes to survive in hostile or adverse conditions.

In the biofilm unit, which is a colony of spirochetes, the spiral form is often lost and is replaced by cystic forms, granular dot forms, or L-forms. So that makes all of the previous biological discussion that I've just reviewed very relevant, and very meaningful. It helps to understand that a group of spirochetes with the DNA and the potential to cause disease can exist without having a single spiral form at all, but they have other diverse forms as they unite into a colony to survive under adverse conditions.

Biofilms are very resistant to antibiotic treatment, and they are resistant to killing, and we've found biofilms in cases of European Lyme Borreliosis, which is the skin manifestation: Acrodermatitis chronica atrophicans (ACA).

Studies that have been done in Europe have shown that colonies of Borrelia spirochetes are present in the skin, and people have had a condition called acrodermatitis chronica atrophicans (ACA), a condition where the skin gets very thin and very fragile, and it persists for many years, and is one of the late manifestations of Lyme disease in the skin. It occurs about thirty years after you've been infected. It's associated with the European form. It isn't very common over here. At least people don't think it is.

ACA contains groupings or colonies of Borrelia, and we have shown that those groupings or colonies are actually Borrelia biofilms. Biofilms are one of the ways that bugs survive in a hostile environment for long periods of time in nature, or in the human body, or in niches where they want to establish themselves."

Hostile environments to the bug are the body's immune system and antibiotics?

"Yes, all those things are hostile to the bug, and the bug then pulls out its bag of tricks different things to help it survive under those conditions. Most of the antibiotics we have today in medicine are derived from soil bacteria. People will go around the world and collect samples of soil and they'll grow the bugs, and they'll look for new antibiotics produced by those bugs, or actual chemical products that interfere with the growth of other bacteria. So, antibiotics are usually derived from bacteria designed to kill or suppress other bacteria in their immediate environment.

So, it makes sense that biofilms would produce substances that create a hostile environment for other bugs in the general area where the biofilm is, so that only the bacteria inside the biofilm are able to survive, and do their biological functions.

They've shown that the resistance inside the biofilm to antibiotics that might be coming in from the outside is markedly increased, and bugs that would normally be killed by one unit are not killed at all, and they might not be killed by a thousand units as long as they stay inside the biofilm, which is like a gelatinous wrapping around colonies of bugs which keep the antibiotics from getting into the center to kill the bugs that are there.

Biofilm looks like a film, and it has potential to protect the bugs inside the film from outside hostile environments, including antibiotics."

A new biology for Lyme disease

"So, all of this is very, very relevant to how we think about a 'new biology' for Lyme disease. If you boil down everything that I have tried to do in my career, it comes down to making a case for a new biology of this bacteria. A biology which includes various forms, various groupings or biofilms, survival of these bugs inside the human body, both inside cells and outside of cells, and the longterm capability of these living organisms to create diseased conditions of various types in the human body, just like syphilis did when it was a major public health problem.

Syphilis could involve any organ system in the body. When people in the 17th, 18th, 19th century had syphilis, they would not all get the same medical conditions, they would get a variety of medical conditions. And they would not all get the same neurological conditions, they would have a variety of conditions. And one of them was dementia, which was called General Paresis.

Variability of the bug, variability of the infection in the organ system, clinical symptoms, and variability of outcomes is just one of the things that makes syphilis a very interesting infection to study, and makes Borrelia very interesting to study, using that model to help us think about how Borrelia can cause problems in the human arena.

So, the research makes for very interesting reading, and it gives people an opportunity to relearn from the model of syphilis, reacquaint themselves with the diversity, the variety, the difficulty in treating and curing syphilis. Many of those things are very similar to the problems we face in understanding and trying to treat and cure Borrelia infections in this century. It's not much of a leap, it's just a sidestep."

Lyme is generally thought to be passed on through ticks, however there are other means. How is Lyme disease passed on?

"It can happen through 'vertical transmission' from mother to fetus, and it happened in syphilis. It does happen in certain people who have Borrelia infection. It goes across the placenta and can cause trouble in the fetus. That autopsy work I did, way back in the eighties, has been published and is out there for people to look at."

What's the difference between active Borrelia infection and dormant infection?

"It might be thought of as infection causing tissue injury. So, as the infection is in the body in any of its forms, and the person who has that infection experiences tissue injury, that is active infection, as opposed to dormant infection, where the infection is in the body but doesn't cause any tissue injury, and the patient doesn't have any symptoms, but because it's in the body it has the capacity to reactivate at a future time. That's how you get across a twenty, thirty, forty year period, to late tertiary manifestations. People may have dormant infection that don't flare up again until late in life, when the immune system, or other factors allow that infection to reactivate.

One of the best examples of that is shingles. People who have had Chicken Pox as a child at age five can have, late in life, reactivation of that virus that's been in the body in a dormant form, and then blisters in the skin will develop in their sixties, sixties, seventies, or eighties, and they'll have a reactivation of that viral infection which entered the body when they were five years old. And it's an example of a dormant or latent infection in the body which only flares up many years, or decades, after it entered the body.

Syphilis can do that, Borrelia can do that, Chicken Pox can do that, other infections can do that. So it's not a controversial topic. It's only controversial when you apply it to Lyme disease. People don't like to put that together with Lyme disease, but it is a very reasonable and very valid association that infections can reactivate."

In your view, why is the recurrence of Lyme infection controversial?

"We live in an arena where there are political, as well as scientific and medical discussions. And I think that scientific and medical discussions are important, and political discussions sometimes prevent us from getting very far with our science and our medicine. As long as people enter an opportunity for discussion and dialog with preconceived notions about what they will and will not embrace as an idea, you have a political weight that is dragging down the level of the opportunity to learn from discussion or from listening to patients.

If people decide that there is no such thing as maternal fetal transmission in Lyme disease, then they can't learn very much when they read my paper, because my paper does show that there is tissue evidence of the infection in newborns that were stillborn, or fetuses that didn't make it to full term.

And there are opportunities to read other papers and not understand how dormant conditions can exist for twenty or thirty years, such as the ACA model in Europe. If you enter the discussion with a preconceived notion of what you will or will not take away from the discussion, you can't learn. So politics is an unfortunate mindset, where the mind is closed before the discussion begins. And that's where a lot of, I think, the politics of discord come from in discussing this, or any other infection.

You know, in the early days of HIV infection, there was a certain reluctance to see it as a public health problem that we know now HIV infections are, in a worldwide basis. But back in the early eighties, when I was beginning my practice, there wasn't a lot of open mindedness about the need to treat HIV as a medical problem. It was a political problem for people who came from Haiti, or for people who lived in San Francisco who happened to be gay. It was a political problem.

Now, we have gotten past that and we see that HIV is a chronic infection. It's a medical issue, not a political issue anymore. Sometimes it takes a long time for politics to exit, and for medicine and science to get back on an even keel."

How long might it take before Lyme becomes less political and more of a medical issue?

"Well, we want to learn from every patient that we can. When Dr. Alzheimer was alive, he wrote about two people with the disease. His first patient was a woman, August D. Then later, before he died prematurely, but he died. Shortly before that he had written about another case history from Alzheimer's.

Now, two cases do not make a very satisfactory platform for describing a new public health epidemic of dementia, which is what we face today. But at the time of Alzheimer's life, there were only two cases. So, sometimes offer a platform for us to understand a problem major public health problem in every continent on this planet.

So sometimes new ideas which emerge from the study of one or two or three cases offer a platform for us to understand major public health problems. So, carefully studied cases, even though they're small and they don't have a lot of statistical weight, sometimes do help us to understand, if you're allowed to think without politics getting in the way of thinking, and clouding your vision."

Where is your research taking you now?

"I'm using DNA probes now, I think that antibodies are very good, but antibodies don't have the great precision that DNA probes do. So I'm using DNA labeled with florescent dyes to eevaluate biofilms of Borrelia to evaluate tissues of those who have died from Alzheimer's. I'm going to use those probes to identify patterns of infection in those two categories: The biofilm category, which is the grouping of the colonies of the bacteria in test tubes or in human tissue, and the Alzheimer work of course, to take autopsy brain tissue, and evaluate that with the DNA probes, to see where the probes light up, and to see if we can find more like Mr. Christensen's case, lit up those Alzheimer's plaques, or those rounded areas of injury in the brain, and develop a larger series of cases to present to the scientific and medical community."

[Please note: Go to www.molecularalzheimer.org, for pictures, research papers, lectures, as well as podcast interviews which he has conducted with Clinical Neurology News, where he discusses the research results as well as the reasoning behind his research. Dr. MacDonald will be speaking at the University of New Haven in May, presenting his findings regarding biofilms of Borrelia with Dr. Eva Sapi, another leading researcher in the area who has some very interesting work to tell us about.]

Dr. MacDonald, thank you for talking with us about your work

"I hope that some of this research will pay off at the patients' medical visits or at the bedside of the patient in the hospital. That's the goal of research, to make a difference in how people are evaluated and treated. And if some people can benefit from Lyme research, and Lyme mimicking Alzheimer's disease, then I think the research will have fulfilled its purpose, which is to try to find a group of people who could benefit from antibiotic therapy, and not go on to die from Alzheimer's disease. That would be a wonderful opportunity.

Thank you so much, and all good wishes."

Dr. MacDonald's website is http://www.molecularalzheimer.org. Go there to see images from his research, and find links for access to his research papers and further information about his work. He spoke with us about the significance of his research on April 6, 2008.

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VIDEO borreliabakteeri/dementia/Alzheimer:


http://www.youtube.com/watch?v=szIL3p0gYoI

Images of Borrelia DNA in Alzheimer's Disease brain tissue- Including Specific DNA probes for Borrelia Flagellin DNA ( A DNA sequence which is NOT present in the human genome) which glows Green wh...

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Alzheimerin taudin merkit voi nähdä silmästä
Julkaistu: 08:26

Jani Kaaro

HELSINGIN SANOMAT

Alzheimerin taudille tyypillistä amyloidiplakkia on löydetty ensimmäistä kertaa silmän verkkokalvolta. Löytö tarjoaa uutta toivoa sairauden varhaisemmasta diagnoosista.

Alzheimerin taudin hoidon suurimpana ongelmana pidetään liian myöhäistä diagnoosia. Kun ensimmäiset oireet ilmenevät, sairaus on voinut edetä kaikessa hiljaisuudessa jo kymmeniä vuosia ja hermosolujen tuhoutuminen on pitkällä. Koska aivoihin kertyvää amyloidiplakkia - jota pidetään taudin tunnusmerkkinä - ei voi havaita suoraan, diagnoosi voidaan varmistaa vasta ruumiinavauksessa.

Amerikkalaisen Cedars-Sinai -sairaalan tutkijat ovat nyt löytäneet amyloidiplakkia ensimmäistä kertaa Alzheimerin tautiin kuolleiden potilaiden verkkokalvolta. Amyloidin määrä verkkokalvolla korreloi taudin vaiheen kanssa siten, että mitä pidemmällä sairaus oli, sitä enemmän verkkokalvolla oli amyloidiplakkia.

Havainnon jälkeen tutkijat varmistivat, että amyloidia kertyy verkkokalvoihin myös Alzheimerin tautia sairastavilla hiirillä. Amyloidiplakki saatiin esiin ruiskuttamalla hiirten verenkiertoon kurkumiinia, joka sitoutuu plakkiin ja värjää sen. Nämä kokeet osoittivat, että hiirillä amyloidiplakin kertyminen verkkokalvoille alkoi paljon ennen oireiden ilmaantumista. Jos näin tapahtuu myös ihmisillä, verkkokalvon amyloidi voi tarjota tehokkaan keinon tunnistaa Alzheimerin tauti ajoissa.

Tutkimus julkaistiin NeuroImage-sarjassa ja sitä esitellään tarkemmin suuressa Alzheimer-konferenssissa heinäkuussa.

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Tutkimuksissa on havaittu kroonisten spirokeettabakteerien aiheuttamien infektioiden voivan aiheuttaa etenevä dementiaa, aivojen surkastumista jne neurosyfilistä sairastavilla.

Viimeaikaisissa tutkimuksissa on havaittu muidenkin spirokeettojen, kuten borrelia-bakteerin, olevan yhteydessä mm Alzheimerin tautiin.

Spirokeettojen aiheuttamat infektiot ovat tapahtuneet vuosia jopa vuosikymmeniä ennen dementia-oireiden alkamista. Dementia saattaa olla ehkäistävissä riittävällä antibiootti ja anti-inflammatoorisella lääkityksellä. (2011)

J Neuroinflammation. 2011 Aug 4;8(1):90. [Epub ahead of print]

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following

Koch's and Hill's criteria.

Miklossy J.

ABSTRACT: It is established that chronic spirochetal infection can cause slowly

progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis.

Recently it has been suggested that various types of spirochetes, in an analogous

way to Treponema pallidum, could cause dementia and may be involved in the

pathogenesis of Alzheimer's disease (AD). Here, we review all data available in

the literature on the detection of spirochetes in AD and critically analyze the
association and causal relationship between spirochetes and AD following

established criteria of Koch and Hill. The results show a statistically

significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95%

CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes

were used, or the highly prevalent periodontal pathogen Treponemas were analyzed,

spirochetes were observed in the brain in more than 90% of AD cases. Borrelia

burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13

times more frequent in AD compared to controls. Periodontal pathogen Treponemas

(T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium,

T. socranskii) and Borrelia burgdorferi were detected using species specific PCR

and antibodies. Importantly, co-infection with several spirochetes occurs in AD.

The pathological and biological hallmarks of AD were reproduced in vitro. The

analysis of reviewed data following Koch's and Hill's postulates shows a probable

causal relationship between neurospirochetosis and AD. Persisting inflammation

and amyloid deposition initiated and sustained by chronic spirochetal infection

form together with the various hypotheses suggested to play a role in the

pathogenesis of AD a comprehensive entity. As suggested by Hill, once the

probability of a causal relationship is established prompt action is needed.

Support and attention should be given to this field of AD research.

Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.




PMID: 21816039 [PubMed - as supplied by publisher]

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Alzheimer voi olla infektion aiheuttama ja jopa tarttuva tauti. Tutkijat antoivat hiirille Alzheimeria sairastaneiden aivokudosta. Hiiret sairastuivat tautiin. Kun hiiret saivat terveiden ihmisten aivokudosta ne eivät sairastuneet. (2011)

Alzheimer's may be transmissible, study suggests


Advertise | AdChoices
By MyHealthNewsDaily Staff
updated 10/4/2011 7:27:53 PM ET

In some cases, Alzheimer's disease may in fact be the result of an infection, and may even be transmissible, a new study in mice suggests.

In the study, mice injected with human brain tissue from Alzheimer's patients developed Alzheimer's disease. The mice developed brain damage characteristic of Alzheimer's disease, and over time, the damage spread throughout their brains, the researchers said.

Mice injected with brain tissue from healthy humans showed no signs of the disease.

"Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process," similar to the way mad cow disease arises from infection with diseased proteins called prions, said study researcher Claudio Soto, a professor of neurology at The University of Texas Medical School at Houston.

MyHealthNewsDaily
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"The underlying mechanism of Alzheimer's disease is very similar to the prion diseases," Soto said. "It involves a normal protein that becomes misshapen, and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer?s," he said.

However, the new findings are very preliminary and it's unclear if the same thing could happen in people. Moreover, the transmission occurred under highly artificial conditions that a person would likely not experience.

The researchers are currently setting up experiments to determine whether the same transmission can occur under more natural routes of exposure, Soto said.
Advertise | AdChoices

The study was published today (Oct. 4) in the journal Molecular Psychiatry.

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Krooniset spirokeettojen aiheuttamat sairaudet voivat aiheuttaa hitaasti etenevän dementian. Esim. Alzheimerin tauti on voimakkaasti yhteydessä eri spirokeettoihin kuten borrelia-bakteeri ja treponeemat.

Siksi maailmanlaajuisesti on kiinnitettävä huomiota bakteerien yhteyteen dementia-sairauksiin. Taudit ovat mahdollisesti ehkäistävissä antibiooteilla, viruslääkkeillä ja tulehduksia lievittävällä hoidolla.



http://journals.cambridge.org/abstract_ ... 9411002006
Expert Reviews in Molecular Medicine

Expert Reviews in Molecular Medicine (2011), 13: e30
Copyright © Cambridge University Press 2011
DOI: 10.1017/S1462399411002006 (About DOI)
Published online: 20 September 2011

Review Article
Emerging roles of pathogens in Alzheimer disease
Judith Miklossya1 c1

a1 International Alzheimer Research Centre, Prevention Alzheimer Foundation, Martigny-Combe, Switzerland

Abstract

Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a significant association between Alzheimer disease (AD) and various types of spirochete (including the periodontal pathogen Treponemas and Borrelia burgdorferi), and other pathogens such as Chlamydophyla pneumoniae and herpes simplex virus type-1 (HSV-1). Exposure of mammalian neuronal and glial cells and organotypic cultures to spirochetes reproduces the biological and pathological hallmarks of AD. Senile-plaque-like beta amyloid (Aβ) deposits are also observed in mice following inhalation of C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and bacterial and viral DNA and RNA all increase the expression of proinflammatory molecules, which activates the innate and adaptive immune systems. Evasion of pathogens from destruction by the host immune reactions leads to persistent infection, chronic inflammation, neuronal destruction and Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide, indicating that Aβ accumulation might be a response to infection. Global attention and action is needed to support this emerging field of research because dementia might be prevented by combined antibiotic, antiviral and anti-inflammatory therapy.


Correspondence:

c1 Corresponding author: Judith Miklossy, 1921 Martigny-Croix CP 16, 1921, Switzerland. E-mail: judithmiklossy@bluewin.ch

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Alzheimerin tauti - keskushermostossa olevien spirokeetta-bakteerien aiheuttama. (Miklossy 2011)

"On osoitettu kroonisten, spirokeettainfektioiden voivan aiheuttaa keskushermostossa hitaasti etenevän dementian ja amyloidien kertymistä. On esitetty että useat spirokeetat esim. borrelia-bakteeri, kupan aiheuttaja (treponema allidum ) jne ovat Alzheimerin taustalla.
Miklossyn tutkimuksessa analysoitiin kaikki aiheesta julkaistut tutkimukset.

Tutkimuksessa havaittiin vahva yhteys spirokeetta-bakteerien ja dementian välillä. Julkaistuissa tutkimuksissa Borrelia-bakteeria löydettiin 25,3%:n aivoista.

Spirokeettojen aiheuttama infektio on tapahtunut vuosia tai vuosikymmeniä ennen dementia-oireiden alkamista. Koska antibioottihoitoja ja tulehduksia hillitseviä hoitoja on saatavilla, voidaan dementiaa pyrkiä hoitamaan samalla tavoin kuin kuppaa.

full text: http://www.jneuroinflammation.com/content/8/1/90

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria

Judith Miklossy

Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90

Abstract
It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD).
Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of !

AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research.

Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

Keywords:
Alzheimer's disease; bacteria; Borrelia burgdorferi; dementia; infection; Lyme disease; periodontal pathogen; spirochetes; Treponema; syphilis

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Vanhuksen nopea dementoituminen ? syyn selvitys ja onnistunut hoito


Duodecim
2004;120(15):1893-96
Christian Andersson, Clara Nyberg ja Dag Nyman

Tapausselostus

Dementialle löytyy suuri joukko erilaisia syitä. Nopea diagnoosi ja hoito voivat antaa välitöntä lievitystä sekä estää pysyviä neurologisia puutostiloja. Kuvaamme nopeasti dementoituneen, aikaisemmin terveen vanhuksen mutkikasta matkaa takaisin normaalitilaan.

Oma potilas

Aikaisemmin terve ilman vakituista lääkitystä oleva yksin asuva 83-vuotias rouva hakeutui joulun aikaan vuonna 2001 keskussairaalan päivystykseen. Hän oli syksyllä auttanut ahkerasti poikaansa omenankorjuussa. Viime kuukausien aikana hän oli käynyt terveyskeskuksessa tutkimuksissa huimauksen takia. Paino oli laskenut 5?7 kg, ja potilaalle oli ilmaantunut käsien vapinaa. Kävelykin oli huonontunut: jalat laahasivat. Huimaus oli pahentunut ja tasapaino huonontunut viikon aikana. Potilas oli kaatunut istualtaan ja pudonnut tuolista. Hän oli myös nähnyt kaksoiskuvia viimeisten kahden päivän aikana.

Päivystyspoliklinikassa havaittiin Rombergin testi taaksepäin kaatavaksi ja kävely horjuvaksi. Potilas otettiin sisätautiosastolle, ja virtsatieinfektiota hoidettiin norfloksasiinilla ja dehydraatiota korjattiin. Potilas kuntoutui rollaattorilla käveleväksi puolessatoista viikossa. Pään tietokonetomografiassa (TT) 24.12. todettiin symmetrisiä periventrikulaarisia leukoaraioosin kaltaisia muutoksia ja lievää sentraalista atrofiaa. Potilaalta otettiin laboratorionäytteitä paikallisten sairaalarutiinien mukaisesti. Hänet kotiutettiin ennen kaikkien vastauksien saapumista.

Potilas hakeutui 25.2.2002 uudelleen päivystykseen. Hän oli tammikuussa joutunut palvelutaloon jaksopaikalle etenevien muistiongelmien, kävelyvaikeuksien, virtsankarkailun, väsymyksen ja heikentyneen yleistilan takia. Kliinisessä tutkimuksessa havaittiin jonkin verran ko-operaatio-ongelmia, oikean käden laskeutumistaipumus peruskokeessa, lievä intentiovapina molemmissa käsissä ja vaikeuksia suorittaa tarkkuuskokeita. Pään TT:ssä todettiin jälleen leukoaraioosimuutoksia. Kolmas aivokammio ja sivukammiot olivat lievästi laajentuneet, mikä sopi sentraaliseen atrofiaan. Päivystäjä epäili kliinisesti normaalipaineista hydrokefalusta ja konsultoi puhelimitse yliopistosairaalan neurokirurgian päivystäjää. Tämän mukaan kyseessä olisi voinut olla normaalipaineinen hydrokefalus. Potilaalle tehtiin lähete yliopistosairaalaan ja TT-kuvat lähetettiin yliopistosairaalan neuroradiologille. Potilas palasi suoraan palvelutaloon odottamaan kutsua yliopistosairaalaan.

Odotettaessa pääsyä neurokirurgiselle osastolle potilaan tilanne huononi edelleen. Potilaan poika painosti »lisätutkimuksiin» ja halusi yliopistosairaalaan pääsyä. Tämän takia potilas lähetettiin 30.5. palvelutalosta päivystykseen. Hänen yleistilansa oli heikentynyt nopeasti. Hän pystyi liikkumaan ainoastaan kahden henkilön avustamana. Virtsankarkailu oli häiritsevää. Potilasta jouduttiin syöttämään, ja hän vietti päivänsä lähinnä istumalla tuolissa. Hänet otettiin sisätautiosastolle, ja siellä todettiin jäykkyyttä kaikissa raajoissa ja kommunikaation hidastuneisuutta. Pään TT:ssä 31.5. todettiin kolmas aivokammio ja sivukammiot lievästi laajentuneiksi. Aivokammion ympärillä näkyi kohtalaisia leukoaraioosimuutoksia. Vasemmalla nucleus lentiformiksessa näkyi senttimetrin läpimittainen infarktiksi sopiva alue. Koska TT-löydökset eivät kunnolla sopineet normaalipaineiseen hydrokefalukseen ja pääsy yliopistosairaalaan viipyi, tehtiin 3.6. »tapping-testi» sunttileikkauksen hyödyllisyyden selvittämiseksi. Siinä poistettiin 40 ml aavistuksen kellertävää likvoria. Testin jälkeen potilaan askel oli suunnilleen entisen pituinen, mutta hän oli virkeämpi.

Likvorianalyysissä todettiin yllättäen meningeaalinen ärsytystila (taulukko, kuva 1). Seerumin borrelia-IgG-vasta-aineet olivat lisääntyneet huomattavasti joulun aikaan huomiotta jääneeseen määritystulokseen verrattuna. Muut dementoitumisen hoidettavat syyt suljettiin pois. Perusverenkuva, elektrolyytit, TSH:n, ionisoituneen kalsiumin, B12-vitamiinin, folaatin, kardiolipiini-vasta-aineiden, TBE-vasta-aineiden ja virusvasta-aineiden pitoisuudet sekä lasko olivat normaalit. Verenglukoosin paastoarvo oli 6,6 mmol/l.

Heti alustavien likvorivastauksien saavuttua aloitettiin neuroborrelioosiepäilyn takia keftriaksonilääkitys 2 g x 1 laskimoon. Hoitoa jatkettiin 14 päivää, ja sen jälkeen potilas sai vielä suun kautta amoksisilliinia 500 mg x 3 kolmen kuukauden ajan. Anamneesissa oli useita punkin puremia mutta ei erythema migransin kaltaista ihottumaa.

Hoidon alussa rekisteröity EEG oli patologinen. Siinä näkyi lievää tai kohtalaista yleistä hidastumista, joka sopi dementiakehitykseen tai meningoenkefaliittiin. Fokaalisia muutoksia ei todettu. Kesäkuun 6. päivänä tehdyssä CERAD-testissä sanalistan tunnistaminen onnistui normaalisti mutta kielensujuvuus, nimeäminen, MMSE -testin tulos (18/30 pistettä), sanalistan viivästynyt muistaminen ja kellon piirtäminen (kuva 2) olivat epänormaaleja.

Jo keftriaksonihoidon aikana potilaan yleistila kohentui huomattavasti. Hän pystyi kotiutuessaan kävelemään itsenäisesti ja kognitiivinen suorituskyky oli parantunut selvästi. Tilaa pidettiin neuroborrelioosina, ja lähete yliopistosairaalan neurokirurgille perutettiin muutamaa päivää ennen kuin potilas olisi päässyt tutkimuksiin.

Toipumista seurattiin, ja 10.8. tehtiin aivojen varjoainetehosteinen magneettitutkimus. Siinä todettiin laajoja signaalinmuutoksia valkoisessa aivoaineessa, etenkin aivokammioiden ympäriltä (kuva 3). Tällaisia ? kylläkin epäspesifisiä ? muutoksia esiintyy lausunnon mukaan neuroborrelioosin yhteydessä.

Seurantakäynnillä tablettihoidon loputtua syyskuussa potilas todettiin alkutilanteeseen verrattuna virkeäksi. Muistiongelmia ja virtsankarkailua ei enää esiintynyt. Potilaalle jäi muistiaukko talvesta kevääseen. Lievä kävelyhäiriö ja huimaus vaivasivat edelleen. Kävelyssä todettiin pientä horjumista, kääntymiset sujuivat hyvin. Lisäksi potilaalla esiintyi lievää kömpelyyttä sormi-nenätestissä sekä sormi-sormitestissä, etenkin vasemmalla. Seuranta-EEG:ssä kesäkuiset muutokset olivat korjaantuneet. Potilas oli nyt periaatteessa kotikuntoinen, mutta hän oli sopeutunut palvelutaloon hyvin eikä halunnut enää lähteä sieltä. Hän auttoi säännöllisesti palvelutalon muita asukkaita jokapäiväisissä askareissa. Helmikuussa 2003 seerumin borrelia-IgG-vasta-ainepitoisuudet olivat selvästi pienentyneet (taulukko).

CERAD-testissä tammikuussa 2003 MMSE-pistemäärä oli 27/30 ja kellon piirtäminen sujui selvästi paremmin (kuva 2). Kielen sujuvuus oli parempi mutta edelleen lievästi huonontunut, ja nimeäminen samalla tavoin kuin aiemmassa testissä. Viivästynyt sanalistan muistaminen sujui paremmin. Potilas oli hyvin toimintakykyinen ja muistamiskyky ikää vastaava. Päivittäisissä toiminnoissa ei esiintynyt ongelmia.


Pohdinta

Neuroborrelioosin oirekuva on vaihteleva. Oireita voi ilmentyä sekä keskus- että ääreishermostosta. Lymfosytaarinen aivo- tai aivokalvontulehdus on näistä harvinaisempi ja neuroborrelioosin vakavin ilmentymä (Kaiser 1998, Lahdenne ym. 2001). Etenevän dementian, normaalipaineisen hydrokefaluksen ja halvauksen kaltaisen oireiston selvittelyssä tulee pitää mielessä neuroborrelioosi, sekä avohoito- että sairaalapotilasta tutkittaessa, etenkin endeemisillä alueilla (Danek ym. 1996). Dementian taustalla voi olla moninaisia häiriöitä joista mainittakoon degeneratiiviset aivosairaudet, aivoverenkierron häiriöt, aivovammat, likvorikierron häiriöt, aivokasvaimet, keskushermostotulehdukset, aineenvaihdunnanhäiriöt, puutostilat, lääkkeet ja myrkyt (Erkinjuntti ym. 2001).

Neuroborrelioosienkefalopatian syntymekanismi on epäselvä. Kuitenkin katsotaan, että sairauden taustalla ovat vaskuliitti ja neuroimmunomodulaatio ja että tämä ärsytys selkäydinnestetilassa voi myötävaikuttaa normaalipaineisen hydrokefaluksen syntyyn (Danek ym. 1996).

Vakavia neuroborrelioosin tapauksia on kuvattu harvakseen ja anekdoottimaisesti. Oman potilaamme tapaus tuli alkukömpelyyksistä huolimatta hyvin kirjatuksi. EEG:t, tietokone- ja magneettikuvaukset, laboratoriokokeet sekä CERAD-testit osoittivat hyvin hoidon onnistumisen ja varmistivat neuroborrelioosidiagnoosin (kolmannen vaiheen myöhäisborrelioosi).

Etenkin endeemisillä alueilla punkin purema ja borrelioosin mahdollisuus on huomioitava myös vanhuksia tutkittaessa, vaikka he liikkuvat luonnossa nuorempia vähemmän.

Kuvatusta tapauksesta voidaan oppia, että tämänkaltaisten potilaiden rutiinitutkimuksiin pitäisi kuulua selkäydinnesteen tutkiminen.

Opimme myös, että puhelimitse konsultoiminen voi olla vaarallinen tapa ja johtaa hakoteille, koska se antaa helposti haetun kaltaisen vastauksen. Lisäksi tuli esiin, että hoitoketjussa olevien lääkärien ajatukset ja tehdyt tutkimukset eivät aina tule kaikkien tietoon ja täten voivat jäädä huomioimatta.


CHRISTIAN ANDERSSON, sairaalalääkäri
Ålands Centralsjukhus
Medicinska enheten
Pb 17, 22101 Mariehamn
CLARA NYBERG, osastonlääkäri
DAG NYMAN, ylilääkäri
Adv. för inre Medicin
Ålands Centralsjukhus
Pb 17, 22101 Mariehamn

Kirjallisuutta

1. Lahdenne P, Seppälä I, Peltomaa M. Neuroborrelioosi. Duodecim 2001:117:1425?35.
2. Kaiser R.J. Neuroborreliosis. Neurology 1998;245(5):247?55.
3. Danek A, Uttner I, Yoursry T, Pfister HW. Lyme neuroborreliosis disguised as normal pressure hydrocephalus. Neurology 1996;46:1743?5.
4. Erkinjuntti T, Rinne J, Soininen H. Muistihäiriöt ja dementia. Kirjassa: Soinila S, Kaste M, Launes J, Somer H, toim. Neurologia. Jyyväskylä: Kustannus Oy Duodecim, 2001, s. 329.

Artikkelin tunnus: duo94439 (094.439)
© 2010 Suomalainen Lääkäriseura Duodecim

[hanpa]

Hyvä tapausesimerkki. Harvinainen, mutta muistettava ja aivan varmasti alidiagnosoitukin. Hämmästyttävää, että löytää itsesä paljon samaa, tosin ikä vähäisempi ( edes jotain hyvää). No neuroborreliahan tässä on ja II-III asteessa mennään.

[soijuv]

Kansainvälinen Alzheimer järjestö. Puheenjohtajana on sveitsiläinen tri Judith Miklossy. Alla hänen yhteystietonsa ja tutkimuksia eri taudinaiheuttajien ja niiden aiheuttamien tulehdusten yhteydestä tautiin.

PREVENTION ALZHEIMER FOUNDATION
An international foundation

www.preventionalzheimer.org

The foundation is registered in Switzerland
President: Judith Miklossy MD, PhD, DsC
Address: 1921 Martigny-Croix, CP 16, CH-1921, Switzerland
Tel: + 41 27 722 0652; Cell: + 41 79 207 4442

Contact address: judithmiklossy@bluewin.ch

Alzheimerin tauti - infektion aiheuttama sairaus?
http://www.miklossy.ch/
"Kupan aiheuttaja, treponema pallidum, kykenee aiheuttamaan hitaasti etenevän dementian, kroonisen tulehdustilan ja amyloidien kertymisen aivoihin. Vastaavaa amyloidikertymää esiintyy Alzheimerin taudissa. Borrelia-bakteeri on spirokeettoihin kuuluva bakteeri kuten kupan aiheuttajakin.
Yleisesti tunnettua on, että taudinaiheuttajat kykenevät piiloutumaan, muuntumaaan tai heikentämään elimistön immuunipuolustusta. Asiaan ei ole kuitenkaan kiinnitetty riittävästi huomiota viime aikoina. Krooninen infektio aiheuttaa eri henkilöille erilaisia oireita riippuen useista tekijöistä kuten geneettisistä tekijöistä, taudinaiheuttajan virulenssista, ympäristötekijöistä, ravitsemustilasta jne.
Riittävän ajoissa aloitettu antibioottihoito saattaa parhaassa tapauksessa parantaa dementian, kuten kupan kohdalla on havaittu, tai pysäyttää sen etenemisen."

ALZHEIMER'S DISEASE - EMERGING ROLE OF INFECTION
www.preventionalzheimer.org

International Alzheimer Research Center

The realization that pathogens can produce slowly progressive chronic diseases has resulted in a new concept of infectious diseases. A number of chronic diseases are caused by one or more infectious agents: e.g., stomach ulcer is caused by Helicobacter pylorii; chronic lung disease in newborns and chronic asthma in adults are caused by Mycoplasmas and Chlamydia pneumoniae and various pathogens are associated with atherosclerosis and Alzheimer disease.

It has been known from a century that chronic bacterial infections are frequently associated with amyloid deposition and that experimental models of inflammation and amyloidosis can be produced by injecting living or killed bacteria or their toxic components to animals.

It has also been known from a century that chronic bacterial infection can cause dementia. Treponema pallidum, the causative agent of syphilis, causes slowly progressive dementia, cortical atrophy, chronic inflammation and amyloid deposition in the affected brain.

Alzheimer’s disease (AD), the most frequent cause of dementia, is a form of amyloidosis. The pathological mechanisms driving the accumulation of amyloid remain unclear. Bacteria, including spirochetes, are powerful stimulators of inflammation and are amyloidogenic. They were suggested to be contributors in generating and sustaining chronic inflammation and amyloid deposition in Alzheimer’s disease. The concept is not new. Fischer, Alzheimer and their colleagues have discussed the possibility that microorganisms may play a role in senile plaque formation already century ago.

The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells can cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the microorganisms can persist in the infected tissues, resulting in chronic, persistent inflammation. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors, including stress and nutrition are critical determinants of disease expression as well.

Pathogens, in addition to strong lymphoplasmocytic infiltrates, can also induce slowly progressive chronic inflammation with poor or absent lymphoplasmocytic infiltrates (e.g. leprosy, syphilis). Activated macrophages and/or microglia are the principal players in this slowly progressive form of infection, which results in slowly progressive parechymal involvement and tissue atrophy.

Highest priority should be given to this emerging field of research. It may have major implications for public health, treatment, and prevention of Alzheimer disease as adequate anti-bacterial drugs are available. Treatment of a bacterial infection may result in regression and, if started early, prevention of the disease. The impact on reducing health-care costs would be substantial.

As it was the case for paretic dementia in syphilis, one may prevent and eradicate dementia in Alzheimer disease.
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Dr Judith Miklossyn sivuilta:
"A scientist who is also a human being cannot rest while knowledge which might reduce suffering rests on the shelf”

Dr Albert B. Sabin, developer of the oral polio vaccine; http://sabin. [Found and taken from the web-cite of a colleague. Thanks]

www.preventionalzheimer.org


August - September 2011

There is an increasing amount of data that indicates that spirochetes are involved in the pathogenesis of AD. This review presents historic and new data related to the involvement of spirochetes in AD. All positive and negative data are included. The goal was to critically analyze the association and causality between spirochetes and AD, based on the substantial amount of data available and on established criteria of Koch and Hill

F1000 evaluation: "An infectious origin of Alzheimer'sdisease has been suggested for many decades. In a wonderfully synthetic review, a convincing role for neurospirochetesis made. This review opens a new perspective on the pathogenesis of Alzheimer's and other neurodegenerative diseases."

Miklossy J. Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. J Neuroinflammation. 2011 Aug 4;8:90

Abstract

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer’s disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247).

When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro. The analysis of reviewed data following Koch’s and Hill’s postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity.As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

_______________________________

Miklossy J. Emerging roles of pathogens in Alzheimer disease. Expert Reviews of Molecular Medicine 2011 ; 13: e30.

In this review all pathogens (bacteria and viruses) were considered. All positive and negative data were included. In addition to the critical review of available data suggestions for future investigations are included.

Abstract

Chronic spirochetal infection can cause slowly progressive dementia, cortical
atrophy and amyloid deposition in the atrophic form of general paresis. There
is a statistically significant association between various types of spirochete
(including the periodontal pathogens Treponemas and Borrelia burgdorferi),
Chlamydophyla pneumoniae, herpes simplex virus type-1 (HSV-1) IgM levels
and Alzheimer disease (AD). Although there is no significant difference
between the frequency of HSV-1 in AD cases and age-matched controls, the
number of ApoE4 HSV-1 carriers with AD is reported to be significantly higher
compared with disease occurrence in noncarriers. Exposure of mammalian
neuronal and glial cells and organotypic cultures to spirochetes reproduces
the biological and pathological hallmarks of AD. Senile-plaque-like beta
amyloid (Aβ) deposits are also observed in mice following inhalation of
C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is
induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and
bacterial and viral DNA and RNA all increase the expression of
proinflammatory molecules, and activate the innate and adaptive immune
systems. Evasion of pathogens from destruction by the host immune reactions
leads to persistent infection, chronic inflammation, neuronal destruction and
Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide,
indicating that Aβ accumulation might be a response to infection. Global
attention and action is needed to support this emerging field of research
because dementia might be prevented by combined antibiotic/antiviral and
anti-inflammatory therapy.

The accumulated observations clearly show the importance of this emerging field of research, which needs support and attention. This is the goal of the Prevention Alzheimer Foundation.


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August - September 2011

May 2010

Amyloid beta, which is the most important biological marker of Alzheimer's disease, revealed to be an anttimicrobial peptide (AMP) following an excellent team work between several Universities such as Mass. General Institute for Neurodegenerative Disease and Dept. of Neurology, Boston University School of Medicine, Beth Israel Deaconess Medical Center, Uppsala University, Uppsala, Sweden and Boston University, Boston, MA.

Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide. PLoS One. 2010 Mar 3;5(3):e9505

E-mail: tanzi@helix.mgh.harvard.edu

BACKGROUND: The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide data supporting an in vivo function for Abeta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies. CONCLUSIONS/SIGNIFICANCE: Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.


September 2008

There is a strong association between Alzheimer's disease and type 2 diabetes. Recent observations show a seroprevalance of various infectious agents in type 2 diabetes. The association of periodontal disorders, which are polybacterial disorders, with Alzheimer's disease and type 2 diabetes suggests that infection and local inflammation can play an important role in these chronic age related disorders.

The following manuscript shows for the first time that d various chronic bacterial infections and local inflammation can play an important role in type 2 diabetes. Chlamydia pneumoniae, Helicobacter pylorii and spirochetes (probably, as in Alzheimer's disease, various types of spirochetes, including periodontal and intestinal spirochetes ) are amoung the candidate pathogens. Antibiotics together with antiinflammatory drugs may slow down and prevent the disease.

Miklossy J, Martins RN, Darbinian N, Khalili K, McGeer PL. Type 2 diabetes: Local inflammation and direct effect of bacterial toxic products. Open Pathol J, 2008, 2: 86-95.

http://www.bentham-open.org/pages/conte ... TOPATJ.SGM

Abstract:

It has been known for almost a century that amyloidosis is frequently associated with chronic bacterial infection. Islet amyloid deposit is characteristic of type 2 diabetes. Periodontal disease, which is predominantly caused by several Gram negative bacteria, is a risk factor for type 2 diabetes. The goal of the study was to explore whether bacteria or their toxic components may play a role in type 2 diabetes. The pancreas in 22 autopsy cases were analyzed for the presence of lipopolysaccharide (LPS), bacterial peptidoglycan (BPG) and local inflammatory processes. Ten of the cases had clinically diagnosed type 2 diabetes, and 12 were age matched controls. The results of an immunohistochemical analysis showed the presence of LPS and BPG in association with islet amyloid deposits in all the 10 diabetic cases as well as in 3 controls with clinically silent amyloid deposits. Chlamydia pneumoniae and Helicobacter pylori specific antigens were detected in the affected islets in a subset of diabetic patients. Clumps of HLA-DR positive activated macrophages, abundant immunoreactivity to the activated complement components C3d, C4d and C5b-9, the terminal attack complex, and a moderate numbers of T4 and particularly of T8 lymphocytes were present in the pancreas of all diabetic cases. These results suggest that bacteria or their slowly degradable remnants may initiate and sustain chronic inflammation in the pancreas and therefore play a role in the pathogenesis of type 2 diabetes. They also indicate that local immune responses, including activation of the classical complement pathway are important in the pathogenesis of type 2 diabetes. There may also be some involvement of the adaptive immune system. Further investigations are essential since a parallel use of antibacterial and antiinflammatory drugs may prevent or slow down the disease progression.


September 2008

Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis
Journal of Neuroinflammation, 2008; 5: 40 (open access, highly accessed)

http://www.jneuroinflammation.com/content/5/1/40

This work shows the presence and persistence of atypical pleomorphic and cystic forms of Borrelia burgdorferi in the brains of three patients with neuropathologically and serologically confirmed Lyme neuroborreliosis. Borrelia burgdorferi was also cultivated from the brains of these patients. The in vivo observed pleomorphic forms of Borrelia spirochetes were identical to those induced in vitro.

The persistence of these more resistant spirochete forms and their intracellular location in host cells, (neurons and glial cells) may be one of those factors, which are responsible for the long latent stage of the disease and the persistence of Borrelia infection. The results also indicate that Borrelia burgdorferi can induce cellular dysfunction and apoptosis.

The abundant HLA-DR activated microglia and reactive astrocytes in the infected brain are indicative of Borrelia induced chronic local inflammation. The detection and recognition of atypical, cystic and granular forms of Borrelia burgdorferi in infected tissues is essential for the diagnosis and the treatment of Lyme disease as they can occur in the absence of typical spiral Borrelia form.

These results suggest that in such cases an adequate and more prolonged antibiotic therapy may be necessary.


ALZHEIMER DISEASE - THE ATROPHIC FORM OF LATE NEUROSPIROCHETOSES

THE INVOLVEMENT OF SEVERAL TYPES OF SPIROCHETES SHOULD BE CONSIDERED AND ANALYZED IN ALZHEIMER'S DISEASE! BORRELIA BURGDORFERI IS ONLY ONE OF THEM. PERIODONTAL ORAL TREPONEMA SPIROCHETES ARE HIGHLY PREVALENT IN THE POPULATION AT LARGE AND MAY BE FREQUENT CANDIDATES IN ALZHEIMER'S DISEASE. INTESTINAL SPIROCHETES AND SPIROCHETES OF THE UROGENITAL TRACTS AND VARIOUS OTHER BORRELIA SPIROCHETES MAY ALL BE INVOLVED IN ALZHEIMER DISEASE. THEREFORE STUDIES CONSIDERING AND ANALYZING BORRELIA BURGDORFERI ALONE CAN BE DISAPPOINTING. SUCH STUDIES WILL NOT EXCLUDE OR REINFORCE THE INVOLVEMENT OF BORRELIA BURGDORFERI IN ALZHEIMER'S DISEASE.

To analyze the involvement of Borrelia burgdorferi in Alzheimer patients who have a positive serology for Borrelia burgdorferi is essential. If we would like to analyze the involvement of Treponema pallidum in a population with dementia without syphilis we would never succeed, despite that it has been known from a century that this spirochete can cause dementia.

In those studies who failed to show the involvement of Borrelia burgdorferi in Alzheimer's disease, the Alzheimer's patients investigated had no positive serology for Borrelia burgdorferi indicating, these these patients did not suffer from Lyme disease. However in those studies where Borrelia burgdorferi was found to be implicated in Alzheimer's disease, Borrelia spirochetes were cultivated in BSK medium from the brains (MacDonald 1987, Miklossy, 1993, Miklossy 1994, 2004) and/or the patients showed a positive serology for Lyme disease (Miklossy et al., 2004; Miklossy, 2007 ) or a positive PCR for Borrelia burgdorferi (Riviere et al., 2004).

The goal of our initial studies was not to show the involvement of Borrelia burgdorferi alone in Alzheimer's disease but to show that several types of spirochetes of the order Spirochaetales are involved in Alzheimer disease, including Borrelia burgdorferi (Miklossy, 1993). The title of the report clearly indicates: Alzheimer's disease - A spirochetosis? and not Alzheimer's disease - A neuroborreliosis? In addition, the hypothesis was based on the observation, that in the brain of a demented patient with atrophic general paresis - used as positive control for the detection of spirochetes - the silver technique for spirochetes revealed the pathology of Alzheimer's disease. At high magnification the regular spiral form and the atypical forms of Treponema pallidum clearly showed that the plaques are made up of Treponema spirochetes and correspond to spirochetal masses. Recently, the local cortical amyloid deposit in the atrophic form of general paresis was characterized and as in Alzheimer disease it corresponds to beta-amyloid.

Those who were analyzing all types of spirochetes including or periodontal pathogen Treponemas, which are expected to be frequent candidates (Miklossy, 1993; Riviere et al, 2004) detected spirochetes in more than 97% of the Alzheimer's cases analyzed.

It is known that spirochetes frequently co-infect with other bacteria. Therefore, the consideration of co-infecting pathogens in Alzheimer's disease is also important.

The accumulated old historic and new observations and the fact that Fischer (1907) and Alois Alzheimer himself (1911) discussed the possibility that microorgansisms may play a role in the formation of senile plaques in AD indicate that it is an obligation for us to consider that infectious agents may play a role in Alzheimer's disease. Today, to support this emerging field of research is essential, particularly, as adequate therapy is available.


JULY 2008

A new volume "Dementia" appeared in the prestigious Handbook of Clinical Neurology: Vol 89 (3rd series); Series Editors: Aminoff, Boller and Swaab, Elsevier
Editors: Charles Duyckaerts (Lab de Neuropath R Escourolle, Paris, France) and
Irene Litvan (Raymond Lee Lebby Professor of Parkinson Disease Research, Department of Neurology, University of Louisville School of Medicine, Louisville, KY, USA)

Website order: http://www.ingentaconnect.com/search/ar ... 0&index=33

In chapters 71 (Ricardo Nitrini: Clinical and therapeutic aspects of dementia in syphilis and Lyme disease) and 72 (Miklossy J. Biology and neuropathology of dementia in syphilis and Lyme disease) the clinical, pathological and biological aspects of syphilis and Lyme disease are discussed.

In chapter 72 the neuropathology and biology of late neurosyphilis and late neuroborreliosis are described. Evidences are presented that chronic or late Lyme neuroborreliosis exists. The pathological changes of tertiary Lyme neuroborreliosis (parenchymal Lyme neuroborreliosis) are strikingly similar to those occurring in tertiary neurosyphilis, also called chronic or late neurosyphilis.

Dementia and stroke as a consequence of Treponema pallidum and Borrelia burgdorferi infections also occur in the tertiary or late stages of these spirochetal diseases.

In meningovascular neurosyphilis and neuroborreliosis the leptomeninges and leptomeningeal arteries are involved leading to Heubner's arteritis and arterial thrombosis with secondary cerebral infarct (indirect parenchymal involvement). When Treponema or Borrelia spirochetes invade the nervous tissue (direct parenchymal involvement) there is a meningo-encephalitis or encephalitis. Two different forms are distinguished. In the infiltrative form there is a severe lymphoplasmacytic infiltration and in the atrophic form, a poor or absent lymphoplasmacytic infiltration, however, severe gliosis (astro- and microgliosis), neuronal loss and cortical atrophy are present. The pathology of both, the infiltrative and atrophic forms were clinically and pathologically documented in neurosyphilis and Lyme neuroborreliosis.

The cases with chronic or late Lyme neuroborreliosis, illustrated in the chapter, were published in per reviewed, internationally recognized medical journals. Some of them more than 15 years ago. Chronic or late Lyme neuroborreliosis was confirmed by clinical, pathological and serological examinations and Borrelia spirochetes, their species specific antigens and genes were detected in the tertiary lesions in the brain. Improvement of late or chronic neurosyphilis and neuroborreliosis following antibiotic treatment was repeatedly reported both in syphilis and Lyme disease, however the treatment of late or chronic cases are more difficult. Syphilis was virtually eradicated by the use of Penicillin, indicating that we can also eradicate Lyme disease.

Newer approaches to the treatment of Lyme disease should take into account the frequent co-infection with other pathogens and the need of a more prolonged combination therapy, as it is the case in the treatment of tuberculosis. Even in the doubt of tuberculosis the treatment of the patients with "tritherapy" is necessary for 6 months. It should be an example for the future treatment of Lyme disease. Such treatment, as it was the case in tuberculosis and syphilis, will substantially prevent extensive healthcare costs in the future.

__________________________________________________________________________

For the first time in a special issue of the Journal of Alzheimer's Disease (JAD) historic and new obervations are reviewed showing the involvement of infectious agents in Alzheimer's disease.

Chronic inflammation and Amyloidogenesis in Alzheimer’s Disease: The Emerging Role of Infection. Guest Editors: Judith Miklossy and Ralph Martins

http://www.j-alz.com/issues/13/vol13-4.html

www.j-alz.com

http://search.eurekalert.org/e3/query.h ... &rq=0&si=1

http://www.sciencedaily.com/releases/2008/05/

"Researchers Explore the Emerging Role of Infection in Alzheimer’s Disease

May 22, 2008, Amsterdam – A number of chronic diseases are in fact caused by one or more infectious agents. For example, stomach ulcers are caused by Helicobacter pylori, chronic lung disease in newborns and chronic asthma in adults are both caused by Mycoplasmas and Chlamydia pneumonia, while some other pathogens have been associated with atherosclerosis. The realization that pathogens can produce slowly progressive chronic diseases has opened new lines of research into Alzheimer’s disease.
In a special issue of the Journal of Alzheimer’s Disease published May 2008, guest editors Judith Miklossy, from The University of British Columbia, and Ralph N. Martins, from Edith Cowan University and Hollywood Private Hospital, Perth, Western Australia, and a group of experts explore this exciting topic.
Alzheimer’s disease (AD), the most frequent cause of dementia, is a form of amyloidosis. It has been known for a century that dementia, brain atrophy and amyloidosis can be caused by chronic bacterial infections, namely by Treponema pallidum in the atrophic form of general paresis in syphilis. Bacteria and viruses are powerful stimulators of inflammation. It was suggested by Alois Alzheimer and his colleagues a century ago that microorganisms may be contributors in the generation of senile plaques in AD.
The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells may cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the organism can persist in the infected tissues and cause chronic inflammation and amyloid deposition. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors and nutrition are critical determinants of disease expression as well.
In this special issue a series of reviews draws attention to both historic and recent observations related to this emerging field of AD research. The first review shows the importance of chronic inflammation in AD, followed by three articles presenting evidence on the involvement of spirochetes, Chlamydia pneumoniae and Herpes simplex virus type 1 in AD. These are followed by a review of amyloid proteins, which occur in many cellular forms in Eukaryotes and Prokaryotes.
The link between several viral and bacterial infections and the most significant genetic factor for AD, APOE ε4, is discussed in the next review. The link between excessive or misplaced iron and a variety of neurodegenerative diseases and infection is reviewed in the final article.
According to Miklossy and Martins, “The historic and new observations reviewed in this special issue clearly show that high priority should be given for further research in this field as it may have major implications for public health, treatment, and prevention as adequate anti-bacterial and anti-viral drugs are available. Treatment of a bacterial infection and associated viral infection may result in regression and, if started early, prevention of disease. The impact on reducing healthcare costs would be substantial.”

Reviews of the special issue of JAD (abstracts)

Claudia Schwab and Patrick L. McGeer
Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders

Alzheimer and a number of other neurodegenerative diseases are characterized by the presence of reactive microglia and reactive astrocytes in association with the lesions. The classic view that microglia exist primarily in either a resting or activated state needs to be broadened in view of recent results. Resting microglia are in constant activity sampling their surround. Activated microglia may be pro-inflammatory, releasing inflammatory cytokines and other inflammatory mediators, or anti-inflammatory, promoting the healing process. There is evidence that microglial phagocytosis is more powerful in the anti-inflammatory state. Activated astrocytes also have pro-inflammatory and anti-inflammatory properties. In the pro-inflammatory state they release inflammatory cytokines. In the anti-inflammVolume 13, Number 4, IN PRESS - atory state they release various growth factors. In AD and other neurodegenerative diseases, both microglia and astrocytes are in a pro-inflammatory state. From a therapeutic point of view it is desirable to find methods of tipping the balance towards an anti-inflammatory state for both types of glia.


Brian J. Balin, C. Scott Little, Christine J. Hammond, Denah M. Appelt, Judith A. Whittum-Hudson, Hervé C. Gérard, Alan P. Hudson
Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease

Sporadic, late-onset Alzheimer’s disease (LOAD) is a non-familial, progressive neurodegenerative disease that is now the most common and severe form of dementia in the elderly. That dementia is a direct result of neuronal damage and loss associated with accumulations of abnormal protein deposits in the brain. Great strides have been made in the past 20 years with regard to understanding the pathological entities that arise in the AD brain, both for familial AD (~5% of all cases) and LOAD (~95% of all cases). The neuropathology observed includes: neuritic senile plaques (NSPs), neurofibrillary tangles (NFTs), neuropil threads (NPs), and often deposits of cerebrovascular amyloid. Genetic, biochemical, and immunological analyses have provided a relatively detailed knowledge of these entities, but our understanding of the “trigger” events leading to the many cascades resulting in this pathology and neurodegeneration is still quite limited. For this reason, the etiology of AD, in particular LOAD, has remained elusive. However, a number of recent and ongoing studies have implicated infection in the etiology and pathogenesis of LOAD. This review focuses specifically on infection with Chlamydophila (Chlamydia) pneumoniae in LOAD and how this infection may function as a “trigger or initiator” in the pathogenesis of this disease.

Judith Miklossy
Chronic inflammation and amyloidogenesis in Alzheimer's disease – role of spirochetes

Alzheimer's disease (AD) is associated with dementia, brain atrophy and the aggregation and accumulation of a cortical amyloid-β peptide (Aβ). Chronic bacterial infections are frequently associated with amyloid deposition. Bacteria or their toxic components are powerful inflammatory stimulators and are amyloidogenic. It had been known from a century that the spirochete Treponema pallidum can cause dementia in the atrophic form of general paresis where. It is noteworthy that the pathological hallmarks of this atrophic form are similar to those of AD. Recent observations showed that bacteria, including spirochetes contain amyloidogenic proteins and also that Aβ deposition and tau phosphorylation can be induced in vitro or in vivo following exposure to bacteria or LPS. Bacteria or their poorly degradable debris are powerful inflammatory cytokine inducers, activate complement, affect vascular permeability, generate nitric oxide and free radicals, induce apoptosis and are amyloidogenic. All these processes are involved in the pathogenesis of AD. Old and new observations, reviewed here, indicate that to consider the possibility that bacteria, including several types of spirochetes highly prevalent in the population at large or their persisting debris may initiate cascade of events leading to chronic inflammation and amyloid deposition in AD is important, as appropriate antibacterial and antiinflammatory therapy would be available to prevent dementia.

Ruth F. Itzhaki and Matthew A. Wozniak
Herpes Simplex Virus Type 1 in Alzheimer’s disease: The Enemy Within

Alzheimer's disease is a modern scourge and is likely to become increasingly so in the future, with increasing longevity. The disease has been investigated for over one hundred years yet the causes of the disease and of the neuropathological characteristics seen in AD brain are still completely unknown. Evidence for a major causative role of a common virus, herpes simplex virus type 1 (HSV1), acting in combination with a genetic factor – the type 4 allele of the apolipoprotein gene, a known susceptibility factor – is presented here. The characteristics of the virus, some of which make it an especially likely candidate for this role, are described, as are the many precedents for the action of a genetic factor modulating outcome of infection. Various possible ways in which HSV1 might lead to development of AD, such as its up-regulation of various enzymes and in particular certain kinases, its effect on the cell cycle, on autophagy, and its inflammatory and oxidative effects are discussed also. It is concluded that there is strong evidence that the virus is indeed a major factor in AD and therefore there is a strong case for appropriate treatment, and possibly for prevention in the future.

Neal D. Hammer, Xuan Wang, Bryan A. McGuffie, Matthew R. Chapman
Amyloids: Friend or Foe?

Amyloidogenesis is the aggregation of soluble proteins into structurally conserved fibers. Amyloid fibers are distinguished by their resistance to proteinase K, tinctorial properties and β-sheet-rich secondary structure. Amyloid formation is a hallmark of many human diseases including Alzheimer’s, Huntington’s and the prion diseases. Therefore, understanding amyloidogenesis will provide insights into the development of therapeutics that target these debilitating diseases. A new class of ‘functional’ amyloids promises a unique glimpse at how nature has harnessed the amyloid fiber to accomplish important physiological tasks. Functional amyloids are produced by organisms spanning all aspects of cellular life. Herein we review amyloidogenesis, with special attention focused on the similarities and differences between the best characterized disease-associated amyloidogenic protein amyloid-β and the formation of several functional amyloids. The implications of studying functional amyloidogenesis and the strategies organisms employ to limit exposure to toxic intermediates will also be discussed.


Nadezda Urosevic and Ralph N. Martins
Infection and Alzheimer’s disease: The ApoE e4 connection and lipid metabolism

Microorganisms, bacteria and viruses, may infect and cause a range of acute and chronic diseases in humans dependent on the genetic background, age, sex, immune and health status of the host, as well as on the nature, virulence and dose of infectious agent. Late onset Alzheimer’s disease (AD) is a progressive neurodegenerative illness of broad aetiology with a strong genetic component and a significant contribution of age, sex and life style factors. Both infectious diseases and AD are characterised by an increased production of an array of immune mediators, cytokines, chemokines and complement proteins by the host cells as well as by changes in the host lipid metabolism. In this review, we re-examine a dangerous liaison between several viral and bacterial infections and the most significant genetic factor for AD, APOE ε4, and the possible impact of this alliance on AD development. This connection was discussed in the broader context of lipid metabolism and in the light of different capacity of various infectious agents, their toxic lipophilic products and host lipoprotein particles for binding to cell receptor(s).

Angela R. Kamer, Ananda Dasanayeke, Ronald G. Craig, Lidia Glodzik-Sobanska, Miroslow Bry, Mony J. de Leon
Alzheimer’s disease and peripheral infections: The possible contribution from periodontal infections, model and hypothesis

Alzheimer’s disease (AD) affects approximately 4.5 million people in the U.S. and this number will increase as the population ages and the life-span increases. Therefore, of paramount importance is identifying mechanisms and factors that affect the risk of developing AD. The etiology and pathogenic mechanisms for AD have not been defined, although inflammation within the brain is thought to play a role. Consistent with this hypothesis, studies suggest that peripheral infections contribute to the inflammatory state of the central nervous system. Periodontitis is a prevalent, persistent peripheral infection associated with gram negative, anaerobic bacteria that are capable of exhibiting localized and systemic infections in the host. This review offers a hypothetical link between periodontitis and AD and will present possible mechanistic links between periodontitis related inflammation and AD. It will review the pathogenesis of periodontitis and the mechanisms by which periodontal infections may affect the onset and progression of AD. Since periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

Eugene D. Weinberg, Judith Miklossy
Iron withholding: a defense against disease
Excessive and misplaced iron promotes an array of neurodegenerative and endocrine diseases as well as cardiomyopathy, arthropathy, neoplasia and infection. Vertebrates maintain an iron withholding defense system designed to prevent accumulation of redox-active (free) iron in sensitive sites and to sequester the metal in innocuous packages. Numerous genetic, behavioral and environmental factors counteract the defense system. Our increasing awareness of the pathologic roles of iron, as well as of the methods for prevention of iron loading coupled with intensified research and development of tissue specific iron chelator drugs, can be expected to yield marked improvements in human health.

[soijuv]

Tutkijat selvittivät neuroborrelioosia sairastavien amyloidiaineenvaihduntaa. Borreliabakteerin todettiiin vaikuttavan amyloidien aineenvaihduntaan.
Amyloidiaineenvaihdunnassa on todettu poikkeavuuksia Alzheimerin, MS-taudin, SLE:n ja HIV:in kohdallla.

http://www.biomedcentral.com/content/pd ... -10-51.pdf

Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

Niklas Mattsson*, Daniel Bremell, Rolf Anckarsäter, Kaj Blennow, Henrik Anckarsäter, Henrik Zetterberg,and Lars Hagberg

Abstract

Background:
The metabolism of amyloid precursor protein (APP) an
d β-amyloid (Aβ) is widely studied in Alzheimer's
disease, where Aβ deposition and plaque development are
essential components of the pathogenesis. However, the
physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered
cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid
metabolism in patients with Lyme neuroborreliosis (LNB).

Methods:
The first part of the study was a cro
ss-sectional cohort study in
61 patients with acute facial palsy (19 with
LNB and 42 with idiopathic facial pare
sis, Bell's palsy) and 22 healthy controls. CSF was analysed for the β-amyloid
peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor pr
otein (APP) isoforms α-sAPP and β-sAPP. CSF total-tau (T-
tau), phosphorylated tau (P-tau) and neurofilament protein
(NFL) were measured to moni
tor neural cell damage. The
second part of the study was a prospective cohort-study in
26 LNB patients undergoing consecutive lumbar punctures
before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.
Results:
In the cross-sectional st
udy, LNB patients had lower levels of CSF α-sAPP, β-sAPP and P-tau, and higher levels of
CSF NFL than healthy controls and patients with Bell's palsy.
In the prospective study, LNB patients had low levels of
CSF α-sAPP, β-sAPP and P-tau at baseline, whic
h all increased towards normal at follow-up.
Conclusions:
Amyloid metabolism is altered in LNB. CSF levels
of α-sAPP, β-sAPP and P-tau are decreased in acute
infection and increase after treatment. In combination with ea
rlier findings in multiple sc
lerosis, cerebral SLE and HIV
with cerebral engagement, this points to an infl
uence of neuroinflammation on amyloid metabolism.
Background
The trans-membranous protein amyloid precursor pro-
tein (APP) has been intensely studied in Alzheimer's dis-
ease (AD), since it is the source of β-amyloid (Aβ)
peptides, recognized as key-components in AD
pathophysiology [1]. Although ubiquitously expressed,
the physiological role of APP in the adult organism
remains largely unknown. APP may undergo non-amy-
loidogenic cleavage at the α-site, which inhibits formation
of Aβ and releases an extracellular soluble α-sAPP frag-
ment. Alternatively, APP is processed by combined cleav-
ages by β-secretase and γ-secretase, releasing Aβ and β-
sAPP. Aβ peptides vary in length due to variability in the
γ-secretase cleavage site. Although CSF levels of α-sAPP
and β-sAPP generally correlate tightly [2], it is not known
how these pathways are orchestrated
in vivo
. CSF levels of
α-sAPP and β-sAPP are reduced in MS and cerebral sys-
temic lupus erythematosus SLE [3], and even lower levels
are seen in HIV patients with cerebral engagement [4].
Lyme neuroborreliosis (LNB) is caused by a central ner-
vous system (CNS) infection by the tick-borne spirochete
Borrelia burgdorferi
. LNB is often manifested by cranial
nerve engagement, and common clinical findings are
facial nerve palsy and radiculitic pain [5,6]. Common lab-
oratory findings are increased albumin ratio, indicating
impaired blood-brain barrier function, and CSF monocy-
tosis. In this study, we investigated CSF markers of amy-
loid metabolism and neural cell damage in LNB, to
elucidate the influence of neuroinflammation on amyloid
metabolism.
* Correspondence: niklas.mattsson@neuro.gu.se
1
Clinical Neuroc
hemistry Laboratory, Institute of
Neuroscience and Physiology,
Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy,
University of Gothenburg, Mölndal, Sweden
Full list of author information is
available at the end of the article
Mattsson
et al.
BMC Neurology
2010,
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:51
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Page 2 of 7
The project contained two clinical studies. The first
was a cross-sectional study in patients with acute facial
palsy caused by either LNB or idiopathic Bell's palsy. The
second was a longitudinal prospective cohort-study,
where LNB patients were followed with successive lum-
bar punctures to investigate time-dependent biomarker
dynamics.
Methods
Study participants
We enrolled different study participants for the cross-
sectional study and the longitudinal study. Participants
included LNB patients, Bell's palsy patients and controls.
Diagnostic criteria for LNB were: I. Clinical symptoms
consistent with neuroborreliosis and alternative explana-
tions excluded; II Inflammatory CSF with mononuclear
cell count >5 × 10
6
/l and erythrocytes <100 × 10
6
/L; III.
One or more of the following: a) Intrathecal antibody
production against
B burgdorferi sp
. b) Antibodies against
B burgdorferi sp
. in serum. c) Erythema migrans within
three months; and IV. One or more of the following: a)
CSF albumin >400 mg/L. b) Oligoclonal IgG and/or IgM-
synthesis on CSF protein electrophoresis. c) IgG index
(CSF/serum IgG ratio)/(CSF/serum albumin ratio) > .70.
Bell's palsy (idiopathic facial palsy) was defined as acute,
monosymptomatic, unilateral peripheral facial paresis of
unknown etiology. Bell's palsy patients were included as
non-infectious palsy controls.
In the cross-sectional part of the study we investigated
61 patients of whom 19 fulfilled criteria for LNB and 42
were classified as Bell's palsy. Twenty-two individuals for
whom CSF analysis was done because of headache or ver-
tigo, but infection and other diseases were excluded (CSF
albumin and cell count were normal), served as controls.
The longitudinal study included 26 LNB patients with
radiculitic pain and sensory disturbances. In addition, 3
patients had facial palsy, 3 had paraparesis, 1 had paresis
of the accessorius nerve, and 1 had a trigeminus paresis.
There was no overlap with the patients in the cross-sec-
tional study. Ten patients without any neurological disor-
ders, undergoing knee replacements, where CSF was
drawn before surgery (Table 1) served as controls in the
longitudinal study. These subjects are described in detail
elsewhere [7]. All LNB patients were given oral treatment
with doxycycline 200-400 mg daily for 10-14 days, which
is the standard treatment in Sweden [8]. CSF was drawn
before start of treatment and at follow-up. The median
duration between the samplings was 45 days (range 33-
61). All subjects gave informed consent to participate.
The study was approved by the ethics committee of Uni-
versity of Gothenburg.
Sampling
CSF samples were collected by lumbar puncture in the
L3/L4 or L4/L5 interspace. Four mL of CSF was collected
in a polypropylene tube and immediately transported to
the local laboratory for centrifugation at 2.000 g at +4°C
for 10 minutes. The supernatant was pipetted off, gently
mixed to avoid possible gradient effects, and aliquoted in
polypropylene tubes that were stored at -70°C pending
biochemical analyses, without being thawed and re-fro-
zen.
Biochemical procedures
All biochemical analyses were performed at the Clinical
Neurochemistry Laboratory in Mölndal, Sweden, by
experienced laboratory technicians who were blinded to
the clinical diagnoses and other clinical information.
Markers of amyloid metabolism
CSF levels of Aβ38, Aβ40 and Aβ42 were measured using
the MSD
®
Human/Rodent (4G8) Abeta Triplex Assay as
described by the manufacturer (Meso Scale Discovery,
MSD
®
, Gaithersburg, MD, USA). This assay employs the
4G8 antibody to capture Aβ and C-terminal specific anti-
bodies to specifically capture Aβ38, Aβ40 and Aβ42. All
isoforms are detected by SULFO-TAG™-labeled anti-4G8
detection antibody. CSF concentrations of α-sAPP and β-
sAPP were determined using the MSD
®
sAPPα/sAPPβ
Multiplex Assay as described by the manufacturer. This
assay employs the 6E10 antibody to capture α-sAPP and a
neoepitope-specific antibody to capture β-sAPP. Both
isoforms are detected by SULFO-TAG™-labeled anti-APP
antibody p2-1.
Markers of neural cell damage
The axonal damage marker CSF T-tau was measured
using a sandwich ELISA (INNOTEST
®
hTAU-Ag, Innoge-
netics, Ghent, Belgium) specifically constructed to mea-
sure all tau isoforms irrespectively of phosphorylation
status (T-tau), as previously described [9]. CSF concen-
trations of tau phosphorylated at threonine 181 (P-tau)
was measured using a sandwich ELISA (INNOTEST
®
PHOSPHO-TAU(181P), Innogenetics), as previously
described [10]. CSF NFL, which is increased following
damage to large myelinated axon, was analyzed using an
ELISA, as previously described [11]. The detection limit
for the NFL ELISA was 125 ng/L.
Albumin
Quantitative determination of albumin in serum and CSF
was performed using the Behring Nephelometer Analyser
(Behringwerke AG, Marburg, Germany). The CSF/serum
albumin ratio was calculated as: CSF albumin (mg/l)/
serum-albumin (g/l).
Statistical analyses
All statistical calculations were performed using SPSS
15.0 (SPSS Inc, Chicago, USA). As the distribution of
quantitative measures was significantly skewed, statistical
tests involving these variables were conducted using the
Mattsson
et al.
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non-parametric Kuskal-Wallis test for comparisons of
multiple groups and the Mann-Whitney U test for pair-
wise comparisons between groups. Quantitative variables
are presented as median (range). The Spearman correla-
tion coefficient was used for analyses of correlation
between variable levels in different study groups. Statisti-
cal significance was determined at P < .05.
Role of the funding source
The sponsors of the study had no role in study design,
data collection, data analysis, data interpretation, or writ-
ing of the report. The corresponding author had full
access to all the data in the study and had final responsi-
bility for the decision to submit for publication.
Results
In the cross-sectional study all groups were comparable
in age. The only exception was that Bell's palsy patients
were slightly younger than th
e controls (P = .023, Table
1). LNB patients had longer history of neurological symp-
toms before the time of lumbar puncture than Bell's palsy
patients (Table 1).
In the longitudinal study, LNB patients were younger
than the controls (P = .031, Table 1). The median dura-
tion of neurologic symptoms was 7 days longer than in
the cross-sectional study (21 days compared with 28
days). At follow-up, all LNB patients had improved in
their clinical symptoms and their inflammatory reactions
had diminished, with decreased CSF monocytic cell
counts (Table 1).
Amyloid metabolism
In the cross-sectional study, LNB patients had lower α-
sAPP and β-sAPP than the other groups (Figure 1), but
there were no differences in Aβ38, Aβ40 or Aβ42 (Table
2). α-sAPP and β-sAPP correlated to most Aβ peptides in
Bell's palsy patients (R = .47-.60, P ≤ .002) and controls (R
= .42-.55, P < .05; the only exception was α-sAPP and
Aβ38 in controls, where there was a trend towards signif-
icance, R = .40, P = .065), but not in LNB patients (P >
.05).
In the longitudinal study, LNB patients had lower base-
line levels of α-sAPP and β-sAPP (Figure 2) and Aβ pep-
tides than controls (Table 3). α-sAPP and β-sAPP
increased after treatment (Figure 2), while Aβ levels were
unaffected (Table 3). Conversely to what was seen in the
cross-sectional study, α-sAPP and β-sAPP correlated to
all Aβ peptides in LNB in the longitudinal study (R = .71-
.98, P < .001), but not in controls (P > .05).
Table 1: Study participants and routine CSF analysis
a
Group N M/F Age
years
Disease
duration
b
CSF monocytes
×10
6
/L
CSF albumin ratio CSF albumin (mg/l)
mean (range)
Cross-sectional study
Controls 22 9/13 44
(25-67)
-1
(1 - 34)
4.65
(2.7-10.5)
222
(83 - 411)
LNB with
facial palsy
19 11/8 42
(8 - 72)
21 136
(14 - 534)
16.3
c
(3.8-49.9)
861
c
(166 - 2850)
Bell's palsy 42 18/24 36
(16-70)
52
(1 - 39)
4.7
d
(2.3-11.5)
206
d
(114 - 569)
Follow-up study
Controls 10 6/4 63
(51-70)
-Missing data 6.4
(4.7-10.1)
302
(192 - 579)
Baseline Follow-up Baseline Follow-up Baseline Follow-up
LNB 26 17/9 49
(12-74)
28 105
(14-590)
12
(2-21)
15
c
(5.7-49.3)
6.1
e
(4.7-13.6)
816
c
(267-2180)
322
e
(146-707)
CSF, cerebrospinal fluid; LN
B, Lyme neuroborreliosis;
a
data presented as median (range
), if not stated otherwise;
b
any neurologic symptom
including radiculitic pain before study
inclusion, presented
as days (median);
c
P < .001 vs controls;
d
P < .001 vs LNB;
e
P < .001 vs LNB baseline.

[soijuv]

Alzheimerin tautiin sairastuneilta yli 90%:lta löydettiin eri spirokeettoja aivoista. Borreliabakteereita löydettiin 25,3%:lta. Sen lisäksi löydettiin muita esim. suun alueella eläviä spirokeettoja. Infektio on tapahtunut vuosia/vuosikymmeniä ennen dementiaoireiden ilmenemistä. Koska riittäviä antibiootti-ja tulehduksia hillitseviä hoitoja on olemassa, kuten esim. syfiliksen hoidossa, on mahdollista että dementia kyettäisiin hoidoilla estämään.

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria
Judith Miklossy

Correspondence: Judith Miklossy judithmiklossy@bluewin.ch

Author Affiliations
International Alzheimer Research Center, Prevention Alzheimer Foundation, Martigny-Combe, Switzerland
Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90

The electronic version of this article is the complete one and can be found online at:http://www.jneuroinflammation.com/content/8/1/90

© 2011 Miklossy; licensee BioMed Central Ltd
Abstract
It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases.

Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research.

Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.
Keywords:
Alzheimer's disease; bacteria; Borrelia burgdorferi; dementia; infection; Lyme disease; periodontal pathogen; spirochetes; Treponema; syphilis
Introduction
The recognition that pathogens can produce slowly progressive chronic diseases has resulted in a new concept of infectious diseases. The pioneering work of Marshall and Warren has established that Helicobacter pylori (H. pylori) causes stomach ulcer [1]. Also the etiologic agent of Whipple's disease was revealed to be another bacterium, Tropheryma whippeli. Recent reports have documented that infectious agents also occur in atherosclerosis, cardio- and cerebrovascular disorders [2-10], diabetes mellitus [11-16], chronic lung [17-20] and inflammatory bowel diseases[1,21-25], and various neurological and neuropsychiatric disorders [26-31].
Nearly a century ago, Fischer, Alzheimer and their colleagues [32,33] discussed the possibility that microorganisms may play a role in the formation of senile plaques. Historic data indicate that the clinical and pathological hallmarks of syphilitic dementia in the atrophic form of general paresis, caused by chronic spirochetal infection, are similar to those of AD. There is an increasing amount of data that indicates that spirochetes are involved in the pathogenesis of AD. This review presents historic and new data related to the involvement of spirochetes in AD. The goal was to critically analyze the association and causality between spirochetes and AD, based on the substantial amount of data available and on established criteria of Koch [34,35] and Hill [36]
More at website: http://www.jneuroinflammation.com/content/8/1/90

[soijuv]

Kroonisten bakteeri- ja virusinfektioiden merkitys neurologisissa sairauksissa kuten Alzheimer, Parkinson, MS jne.


http://www.bjmp.org/content/role-chroni ... hiatric-au

Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1

Garth L. Nicolson and Jörg Haier
Cite this article as: BJMP 2009:2(4) 20-28
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Abstract

Chronically ill patients with neurodegenerative, neurobehavioral and psychiatric diseases commonly have systemic and central nervous system bacterial and viral infections. In addition, other chronic illnesses where neurological manifestations are routinely found, such as fatiguing and autoimmune diseases, Lyme disease and Gulf War illnesses, also show systemic bacterial and viral infections that could be important in disease inception and progression or in increasing the number and severity of signs and symptoms. Evidence of Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, human herpesvirus-1, -6 and -7 and other bacterial and viral infections revealed high infection rates in the above illnesses that were not found in controls. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of progressive chronic diseases.
Abbreviations: Ab beta amyloid; AD Alzheimer’s disease; ADHD attention-deficit/hyperactivity disorder; ALS amyotrophic lateral sclerosis; ASD autism spectrum disorders; EBV Epstein-Barr virus; CFS chronic fatigue syndrome; CFS/ME chronic fatigue syndrome/myalgic encephalomyopathy; CI confidence interval; CMV cytomegalovirus; CSF cerebrospinal fluid; CNS central nervous system; ELISA enzyme linked immunoabsorbant assay; GWI Gulf War illnesses; HHV human herpes virus; HSV herpes simplex virus; PCR polymerase chain reaction; PD Parkinson’s disease


Introduction

Chronic infections appear to be common features of various diseases, including neurodegenerative, psychiatric and neurobehavioral diseases, autoimmune diseases, fatiguing illnesses and other conditions.1-4 Neurodegenerative diseases, chronic degenerative diseases of the central nervous system (CNS) that cause dementia, are mainly diseases of the elderly. In contrast, neurobehavioral diseases are found mainly in younger patients and include autism spectrum disorders (ASD), such as autism, attention deficit disorder, Asperger’s syndrome and other disorders.5 For the most part, the causes of these neurological diseases remain largely unknown.2 Neurodegenerative diseases are characterized by molecular and genetic changes in nerve cells that result in nerve cell degeneration and ultimately nerve cell dysfunction and death, resulting in neurological signs and symptoms and dementia.2,3 On the other hand, neurobehavioral diseases are related to fetal brain development but are less well characterized at the cellular level and involve both genetic and environmental factors.6, 7 Even less well characterized at the cellular and genetic level are the psychiatric disorders, such as schizophrenia, paranoia, bipolar disorders, depression and obsessive-compulsive disorders.

Genetic linkages have been found in neurodegenerative and neurobehavioral diseases, but the genetic changes that occur and the changes in gene expression that have been found are complex and usually not directly related to simple genetic alterations.2, 6-8 In addition, it is thought that nutritional deficiencies, environmental toxins, heavy metals, chronic bacterial and viral infections, autoimmune immunological responses, vascular diseases, head trauma and accumulation of fluid in the brain, changes in neurotransmitter concentrations, among others, are involved in the pathogenesis of various neurodegenerative and neurobehavioral diseases.2, 3, 5-16 One of the biochemical changes found in essentially all neurological, neurodegenerative and neurobehavioral diseases is the over-expression of oxidative free radical compounds (oxidative stress) that cause lipid, protein and genetic structural changes.9-11 Such oxidative stress can be caused by a variety of environmental toxic insults, and when combined with genetic factors could result in pathogenic changes.14

Neurodegenerative diseases

Infectious agents are important factors in neurodegenerative and neurobehavioral diseases and may enter the brain within infected migratory macrophages. They may also gain access by transcytosis across the blood-brain-barrier or enter by intraneuronal transfer from peripheral nerves.15 Cell wall-deficient bacteria, such as species of Mycoplasma, Chlamydia (Chlamydophila), Borrelia and Brucella, among others, and various viruses are candidate brain infectious agents that may play important roles in neurodegenerative and neurobehavioral diseases.16-19 Such infections are systemic and can affect the immune system and essentially any organ system, resulting in a variety of systemic signs and symptoms.4, 15, 16, 19, 20

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset, idiopathic, progressive neurodegenerative disease that affects both central and peripheral motor neurons.21 Patients show gradual progressive weakness and paralysis of muscles due to destruction of upper motor neurons in the motor cortex and lower motor neurons in the brain stem and spinal cord. This ultimately results in death, usually by respiratory failure.21, 22 The overall clinical picture of ALS can vary, depending on the location and progression of pathological changes.23

The role of chronic infections has attracted attention with the finding of enterovirus sequences in a majority of ALS spinal cord samples by polymerase chain reaction (PCR).24 However, others have failed to detect enterovirus sequences in spinal cord samples from patients with or without ALS.25-26 In spite of the mixed findings on enterovirus, infectious agents that penetrate the CNS could play a role in the aetiology of ALS. Evidence for transmission of an infectious agent or transfer of an ALS-like disease from man-to-man or man-to-animals has not been found.27

Using PCR methods systemic mycoplasmal infections have been found in a high percentage of ALS patients.28, 29 We found that 100% of Gulf War veterans from three nations diagnosed with ALS had systemic mycoplasmal infections.28 All but one patient had M. fermentans, and one veteran from Australia had a systemic M. genitalium infection. In nonmilitary ALS patients systemic mycoplasmal infections of various species were found in approximately 80% of cases.28 Of the mycoplasma-positive civilian patients who were further tested for various species of Mycoplasma, most were positive for M. fermentans (59%), but other Mycoplasma species, such as M. hominis (31%) and M. pneumoniae infections (9%) were also present. Some of the ALS patients had multiple infections; however, multiple mycoplasmal infections were not found in the military patients with ALS.28 In another study 50% of ALS patients showed evidence of systemic Mycoplasma species by PCR analysis.29

ALS patients who live in certain areas often have infections of Borrelia burgdorferi, the principal aetiological agent in Lyme disease. For example, ALS patients who live in a Lyme-prevalent area were examined for B. burgdorferi infections, and over one-half were found to be seropositive for Borrelia compared to 10% of matched controls.30 In addition, some patients diagnosed with ALS were subsequently diagnosed with neuroborreliosis.31 Spirochetal forms have been observed in the brain tissue of ALS patients and in patients with other neurodegenerative diseases.32 In general, however, the incidence of Lyme infections in ALS patients is probably much lower. In one recent study on 414 ALS patients only about 6% showed serological evidence of Borrelia infections.33 Some Lyme Disease patients may progress to ALS, but this is probably only possible in patients who have the genetic susceptibility genes for ALS as well as other environmental toxic exposures.34, 35

Additional chronic infections have been found in ALS patients, including human herpes virus-6 (HHV-6), Chlamydia pneumoniae andother infections.36, 37 There is also a suggestion that retroviruses might be involved in ALS and other motorneuron diseases.38 McCormick et al.39 looked for reverse transcriptase activity in serum and cerebrospinal fluid of ALS and non-ALS patients and found reverse transcriptase activity in one-half of ALS serum samples tested but in only 7% of controls. Interestingly, only 4% of ALS cerebrospinal fluid samples contained reverse transcriptase activity.39

Although the exact cause of ALS remains to be determined, there are several hypotheses on its pathogenesis: (1) accumulation of glutamate causing excitotoxicity; (2) autoimmune reactions against motor neurons; (3) deficiency of nerve growth factor; (4) dysfunction of superoxide dismutase due to mutations; and (5) chronic infection(s).24, 27-40 None of these hypotheses have been ruled out or are exclusive, and ALS may have a complex pathogenesis involving multiple factors. 28, 36

It is tempting to propose that infections play an important role in the pathogenesis or progression of ALS.28, 40 Infections could be cofactors in ALS pathogenesis, or they could simply be opportunistic, causing morbidity in ALS patients. For example, infections could cause the respiratory and rheumatic symptoms and other problems that are often found in ALS patients. Since the patients with multiple infections were usually those with more rapidly progressive disease,28 infections likely promote disease progression. Indeed, when Corcia et al.41 examined the cause of death in 100 ALS patients, the main causes were broncho-pneumonia and pneumonia. Finally, there are a number of patients who have ALS-like signs and symptoms but fall short of diagnostic criteria. Although a careful study has not been attempted on these patients, there is an indication that they have the same infections as those found in patients with a full diagnosis of ALS (personal communication). Thus ALS-like diseases may represent a less progressive state, in that they may lack additional changes or exposures necessary for full ALS.

Multiple sclerosis

Multiple sclerosis (MS) is the most common demyelinating neurological disease. It can occur in young or older people and is a cyclic (relapsing-remitting) or progressive disease that continues progressing without remitting.42 Inflammation and the presence of autoimmune antibodies against myelin and other nerve cell antigens are thought to cause the myelin sheath to break down, resulting in decrease or loss of electrical impulses along the nerve fibers.42, 43 In the progressive subset of MS neurological damage occurs additionally by the deposition of plaques on the nerve cells to the point where nerve cell death occurs. In addition, breakdown of the blood-brain barrier in MS is associated with local inflammation caused by glial cells.42, 43 The clinical manifestations of demyelinization, plaque damage and blood-brain barrier disruptions cause variable symptoms, but they usually include impaired vision, alterations in motor, sensory and coordination systems and cognitive dysfunction.43

There is strong evidence for a genetic component in MS.44, 45 Although it has been established that there is a genetic susceptibility component to MS, epidemiological and twin studies suggest that MS is an acquired, rather than an inherited, disease.46

MS has been linked to chronic infection(s).46, 47 For example, patients show immunological and cytokine elevations consistent with chronic infections.48-50 An infectious cause for MS has been under examination for some time, and patients have been tested for various viral and bacterial infections. 44, 45,47, 48, 51 One of the most common findings in MS patients is the presence of C. pneumoniae antibodies and DNAin their cerebrospinal fluid.51-53 By examining relapsing-remitting and progressive MS patients for the presence of C. pneumoniae in cerebrospinal fluid by culture, PCR and immunoglobulin reactivity Sriram et al.52 were able to identify C. pneumoniae in 64% of MS cerebrospinal fluid versus 11% of patients with other neurological diseases. They also found high rates (97% positive) of PCR-positive MOMP gene in MS- patients versus 18% in other neurological diseases, and this correlated with 86% of MS patients being serology-positive patients by ELISA and Western blot analysis.52 Examination of MS patients for oligoclonal antibodies against C. pneumoniae revealed that 82% of MS patients were positive, whereas none of the control non-MS neurological patients had antibodies that were absorbed by C. pneumoniae elemental body antigens.53 Similarly, Contini et al.54 found that the DNA and RNA transcript levels in mononuclear cells and cerebrospinal fluid of 64.2% of MS patients but in only 3 controls.

Using immunohistochemistry Sriram et al.55 later examined formalin-fixed brain tissue from MS and non-MS neurological disease controls and found that in a subset of MS patients (35%) chlamydial antigens were localized to ependymal surfaces and periventricular regions. Staining was not found in brain tissue samples from other neurological diseases. Frozen tissues were available in some of these MS cases, and PCR amplification of C. pneumoniae genes was accomplished in 63% of brain tissue samples from MS patients but none in frozen brain tissues from other neurological diseases. In addition, using immuno-gold-labeled staining and electron microscopy they examined cerebrospinal fluid sediment for chlamydial antigens and found that the electron dense bodies resembling bacterial structures correlated with PCR-positive results in 91% of MS cases.55 They also used different nested PCR methods to examine additional C. pneumoniae gene sequences in the cerebrospinal fluid of 72 MS patients and linked these results to MS-associated lesions seen by MRI.56

MRI was used by Grimaldi et al.57 to link the presence of C. pneumoniae infection with abnormal MRI results and found linkage in 21% of MS patients. These turned out to be MS patients with more progressive disease.58 In addition, higher rates of C. pneumoniae transcription were found by Dong-Si et al.58 in the cerebrospinal fluid of 84 MS patients. The data above and other studies strongly support the presence of C. pneumoniae in the brains of MS patients,59-61 at least in the more progressed subset of MS patients.

Other research groups have also found evidence for C. pneumoniae in MS patients but at lower incidence. Fainardi et al.62 used ELISA techniques and found that high-affinity antibodies against C. pneumoniae were present in the cerebrospinal fluid of 17% of MS cases compared to 2% of patients with non-inflammatory neurological disorders. They found that the majority of the progressive forms of MS were positive compared to patients with remitting-relapsing MS. The presence of C. pneumoniae antibodies was also found in other inflammatory neurological disorders; thus it was not found to be specific for MS.62

In contrast to the studies above, other researchers have not found the presence of C. pneumoniaeor other bacteriain the brains of MS patients.63-65 For example, Hammerschlag et al.66 used nested PCR and culture to examine frozen brain samples from MS patients but could not find any evidence for C. pneumoniae. However, in one study C. pneumoniae was found at similar incidence in MS and other neurological diseases, but only MS patients had C. pneumoniae in their cerebrospinal fluid.64 Swanborg et al.67 reviewed the evidence linking C. pneumoniae infection with MS and concluded that it is equivocal, and they also speculated that specific genetic changes may be necessary to fulfill the role of such infections in the aetiology of MS.

Another possible reason for the equivocal evidence linking MS with infections, such as C. pneumoniae, is that multiple co-infections could be involved rather than one specific infection. In addition to C. pneumoniae found in most studies, MS patients could also have Mycoplasma species, B. burgdorferi and other bacterial infections as well as viral infections.68 When multiple infections are considered, it is likely that >90% of MS patients have obligate intracellular bacterial infections caused by Chlamydia (Chlamydophila), Mycoplasma, Borrelia or other intracellular bacterial infections. These infections were found only singly and at very low incidence in age-matched subjects.68 In spite of these findings, others did not find evidence of Mycoplasma species in MS brain tissue, cerebrospinal fluid or peripheral blood.69

Viruses have also been found in MS. For example, HHV-6 has been found at higher frequencies in MS patients, but this virus has also been found at lower incidence in control samples.70 Using PCR Sanders et al.70 examined postmortem brain tissue and controls for the presence of various neurotrophic viruses. They found that 57% of MS cases and 43% of non-MS neurological disease controls were positive for HHV-6, whereas 37% and 28%, respectively, were positive for herpes simplex virus (HSV-1 and -2) and 43% and 32%, respectively, were positive for varicella zoster virus. However, these differences did not achieve statistical significance, and the authors concluded “an etiologic association to the MS disease process [is] uncertain.” They also found that 32% of the MS active plaques and 17% of the inactive plaque areas were positive for HHV-6.70 Using sequence difference analysis and PCR Challoner et al.71 searched for pathogens in MS brain specimens. They found that >70% of the MS specimens were positive for infection-associated sequences. They also used immunocytochemistry and found staining around MS plaques more frequently than around white matter. Nuclear staining of oligodendrocytes was also seen in MS samples but not in controls.71 Using immunofluorescent and PCR methods HHV-6 DNA has also been found in peripheral leukocytes in the systemic circulation of MS patients.72, 73 However, using PCR methods, others did not found herpes viruses in the peripheral blood or CSF of MS patients.74, 75 Evidence that prior infection with EBV could be related to the development of MS was proposed; however, EBV infects more than 90% of humans without evidence of health problems and 99% of MS patients.76 The difference in MS patients could be the presence of multiple infections, including EBV. Recently Willis et al.77 used multiple molecular techniques to examine MS tissue but failed to find EBV in any MS tissues but could find EBV in CNS lymphomas.

Current reviews and the information above points to an infectious process in MS.47, 48, 75, 76, 78-80 Although a few studies did not come to this conclusion,74, 75 most studies have found infections in MS patients. It is interesting that it is the progressive rather than relapsing-remitting forms of MS which have been associated with chronic infections; therefore, infections might be more important in MS progression than in its inception. Various infections may also nonspecifically stimulate the immune system.47, 48 Infections may also invade immune cells and alter immune cell function in a way that promotes inflammation and autoimmune activity.78 If infections like C. pneumoniae and Mycoplasma species are important in MS, then antibiotics effective against these infections should improve clinical status. Although preliminary, that is in fact what has been seen, but not in all patients.81 As in other neurodegenerative diseases, multiple factors appear to be involved in the pathogenesis of MS.

Alzheimer’s disease

Alzheimer’s Disease (AD) is a family of brain disorders usually found in elderly patients and is the most common cause of dementia. AD is characterized by slow, progressive loss of brain function, notable lapses in memory, disorientation, confusion, mood swings, changes in personality, language problems, such as difficulty in finding the right words for everyday objects, loss of behavioral inhibitions and motivation and paranoia. The course of AD varies widely, and the duration of illness can range from a few years to over 20 years. During this period the parts of the brain that control memory and thinking are among the first affected, followed by other brain changes that ultimately result in brain cell death.82

AD is characterized by distinct neuropathological changes in brain tissues and cells. Among the most notable are the appearance of plaques and tangles of neurofibrils within brain nerve cells that affect synapses and nerve-nerve cell communication. These structural alterations involve the deposition of altered amyloid proteins.83, 84 Although the cause of AD is not known, the formation of the amyloid plaques and neurofibrillary tangles may be due to genetic defects and resulting changes in the structure of beta amyloid proteins. This in turn may be caused by chemicals or other toxic events, inflammatory responses, excess oxidative stress and increases in reactive oxygen species, loss of nerve trophic factors and reductions in nerve cell transmission.83-87

Recently AD brain infections have become important.88-90 For example, one pathogen that has attracted considerable attention is C. pneumoniae.91, 92 As mentioned above, this intracellular bacterium has a tropism for neural tissue, and it has been found at high incidence in the brains of AD patients by PCR and immunohistochemistry.92 C. pneumoniae has also been found in nerve cells in close proximity to neurofibrillary tangles.92, 93 Similarly to Mycoplasma species, C. pneumoniae can invade endothelial cells and promote the transmigration of monocytes through human brain endothelial cells into the brain parenchyma.94 C. pneumoniae has been found in the brains of most AD patients,91 and it has been cultured from AD brain tissue.95 Injection of C. pneumoniae into mice stimulates beta amyloid plaque formation.96 Although the data are compelling, some investigators have not found C. pneumoniae infections in AD.97, 98

AD patients also have other bacterial infections, such as B. burgdorferi.99 Using serology, culture, Western blot and immunofluorenscence methods this Lyme Disease infection has been examined in AD.100, 101 Not all researchers, however, have found evidence of B. burgdorferi in AD patients.102, 103 The presence of intracellular infections like B. burgdorferi in AD patients has been proposed to be a primary event in the formation of AD beta amyloid plaques. This is thought to occur by the formation of “congophilic cores” that attract beta amyloid materials.104 Multiple reports indicate that AD nerve cells are often positive for B. burgdorferi, indicating that this intracellular bacteria could be important in the pathogenesis of AD.99, 100, 104, 105

The hypothesis in AD that intracellular microorganisms could provide “cores” for the attraction of beta amyloid materials is appealing, but other factors, including the induction of reactive oxygen species, lipid peroxidation and the breakdown of the lysosomal membranes releasing lysosomal hydrolases, are also thought to be important in beta amyloid deposition.105 That infections may be important in AD pathogenesis is attractive; however, some negative reports have not confirmed the presence of infections like B. burgdorferi in AD patients.99-101 This suggests that the infection theory, although compelling, remains controversial.102, 105

Herpes virus infections have also been found in AD,especially HSV-1.106, 107 Previously it was determined that HSV-1 but not a related neurotrophic virus (varicella zoster virus) is present more often in AD brains, and this could be linked to AD patients who have the risk factor ApoE e4 allele.108, 109 HSV-1 is thought to be involved in the abnormal aggregation of beta amyloid fragments within the AD brain by reducing the amount of full-length beta amyloid precursor protein and increasing the amounts of their fragments.110 HSV-1 infection of glial and neuronal cells results in a dramatic increase in the intracellular levels of beta amyloid forms, whereas the levels of native beta amyloid precursor protein are decreased.111 This is similar to what has been found in mice infected with HSV-1, indicating that HSV-1 is probably involved directly in the development of senile-associated plaques. Another herpes virus, HHV-6, has also been found in AD patients, but it is thought that this virus is not directly involved in AD pathogenesis. HHV-6 may exacerbate the effects of HSV-1 in AD ApoE e4 carriers.112

Other infections have been found in AD patients, for example, C. pneumoniae, Helicobacter pylori amongst others.113 It has been proposed that such infections may act as a trigger or co-factor in AD.114 Although experimental evidence that pathogens can elicit the neuropathological changes and cognitive deficits that characterize AD is lacking, this approach may yield interesting and important results. These authors also stressed that systemic infections must be considered as potential contributors to the pathogenesis of AD.114

Parkinson’s disease

Parkinson’s disease (PD) is characterized by akinesia, muscular rigidity and resting tremor.103 In addition, autonomic dysfunction, olfactory disturbances, depression, sensory and sleep disturbances and frequently dementia characterize this disease.115 The pathology of PD indicates a progressive loss of the dopamine neurons of the substantia nigra together with the presence of Lewy bodies and alpha-synuclein. More extensive brain degeneration also occurs, from the medulla oblongata to the cerebral cortex.116, 117

Age-related inclusion bodies and protein aggregations or defects in their degradation characteristically occur in PD, but their role in PD pathogenesis remains unclear.117, 118 Some evidence suggests a relationship between PD and specific genetic changes, such as changes in the genes affecting mitochondria, protein degradation, organelle trafficking and vesicular fusion, and in proteins involved in oxidative stress or antioxidant function.102 Inflammation has also been associated with PD pathology.119

The pathogenesis of PD has been proposed to be due to multiple genetic and neurotoxic events that produce oxidative damage and cell death. In the case of PD the relevant targets of toxic events are neuromelanin-containing dopaminergic neurons of the substantia nigra.118, 120 A case-control study indicated that multiple environmental factors and genetic background were statistically related risk factors for PD.121 Prominent among these were long-term toxic exposures and trauma early in life.122 For example,early life exposure to brain injury, chemicals and/or infections may initiate a cyclic inflammatory process involving oxidative damage, excitotoxicity, mitochondrial dysfunction and altered proteolysis that later in life results in substantia nigra neuron death.123, 124

A role for chronic infections in PD pathogenesis has been proposed.123, 124 One infection found in PD that has aroused considerable interest is the presence of chronic gastrointestinal Helicobacter pylori.125 Indeed, treatment of this infection offers relief to late stage cachexia in PD patients receiving L-dopa.126 Helicobacter pylori-infected PD patients showed reduced L-dopa absorption and increased clinical disability,127 whereas treatment of this infection increased L-dopa absorption and decreased clinical disability.128 H. pylori may not be directly involved in the pathogenesis of PD, but its systemic presence could affect the progression and treatment of PD, probably by stimulating inflammation and autoimmunity.128

Chronic infections in PD have been linked to inflammation and autoimmune responses.129-131 Experimental models of PD have been developed using neurological viral or bacterial infections to initiate the pathogenic process.132, 133 Spirochetes have also been found in Lewy bodies of PD patients.30 Other infections, such as viral encephalitis,134 AIDS-associated opportunistic infections of the basal ganglia,135 coronavirus,136 among other infections,68, 137, 138 have been found in PD and could be important in stimulating inflammation and autoimmune responses. It has been stressed that additional research will be necessary to establish whether a causal link exists between PD and chronic infections.139

Neurobehavioral diseases

Autism spectrum disorders

ASD, such as autism, Asperger’s syndrome, etc., are neurobehavioral diseases of primarily the young where patients generally suffer from an inability to communicate properly, form relationships with others and respond appropriately to their environment. Such patients do not all share the same signs and symptoms but tend to share certain social, communication, motor and sensory problems that affect their behavior in predictable ways. These patients often display repetitive actions and develop troublesome fixations with specific objects, and they are often painfully sensitive to certain sounds, tastes and smells.140, 141

ASD cases are likely to be caused by multiple factors, including genetic defects, heavy metal, chemical and biological exposures, among other important events, which are probably different in each patient. ASD patients appear to have similarities in genetic defects and environmental exposures that are important in patient morbidity or in illness progression.5-8, 140-142

Chronic infections appear to be an important element in the development of ASD.6, 16, 143, 144 In ASD patients more than 50 different bacterial, viral and fungal infections have been found,6 some apparently more important than others in causing symptoms. It has been known for some time that ASD patients have a number of nonspecific chronic signs and symptoms, such as fatigue, headaches, gastrointestinal, vision problems, occasional intermittent low-grade fevers and other signs and symptoms that are generally excluded in the diagnosis of ASD but are consistent with the presence of infections.143 Indeed, increased titres to various viruses as well as bacterial and fungal infections have been commonly seen in ASD patients.6, 16, 19, 143-145 Not withstanding these reports, epidemiological evidence for an association of childhood infections in the first two years of life and ASD has been mixed.146

Environmental exposures to chemicals and heavy metals also appear to be important in the development of ASD.140, 141, 147, 148 The relationship between ASD and heavy metals may involve the role of multiple vaccines in ASD pathogenesis.130, 141 ASD patients often show their first signs and symptoms after multiple childhood immunizations, and the sharp increase in Autism rates occurred only after the multiple MMR vaccine came into widespread use.141 In some states in the U.S. children receive as many as 33 vaccines before they can enroll in school.140 Such vaccines can contain mercury and other toxic preservatives, and some may also contain contaminating bacteria, as found in veterinary vaccines.149

There are very few studies that have followed the transmission of infections and subsequent autism. Previously we found that veterans of the Gulf War with chronic fatiguing illnesses (Gulf War illnesses, GWI) exhibited multiple nonspecific signs and symptoms similar to chronic fatigue syndrome/myalgic encephalomyopathy (CFS/ME).150, 151 After returning to the home with GWI, their children subsequently became symptomatic, and these children were often diagnosed with ASD.152, 153 Symptomatic children (mostly diagnosed with ASD) were infected with the same Mycoplasma species, M. fermentans, that was found in the veterans and their symptomatic family members, and this was not seen in aged-matched control subjects or in military families without GWI. In the GWI families some non-symptomatic family members did have mycoplasmal infections (~10%), but this was not significantly different from the incidence of mycoplasmal infections in healthy control subjects.152, 153

Subsequently ASD patients who were not in military families were examined for systemic mycoplasmal infections.153 The majority (~54%) were positive for mycoplasmal infections. However, in contrast to the children of GWI patients who for the most part had only M. fermentans, the civilian children tested positive for a variety of Mycoplasma species. We also tested a few siblings without apparent signs and symptoms, and for the most part few had these infections.153 In another study we examined the blood of ASD patients from Central and Southern California and found that a large subset (>58%) of patients showed evidence of Mycoplasma infections compared to age-matched control subjects (Odds Ratio=13.8, p<0.001).19 ASD patients were also examined for C. pneumoniae (8.3% positive, Odds Ratio=5.6, p<0.01) and HHV-6 (29.2% positive, Odds Ratio=4.5, p<0.01). The results indicated that a large subset of ASD patients display evidence of bacterial and/or viral infections (Odds Ratio=16.5, p<0.001).19

ASD patients have been examined for B. burgdorferi infections.154 Various studies revealed that 22-30% of ASD patients (N=76) have Borrelia infections.6, 154 The incidence of Borrelia infections in ASD patients may be related to Lyme disease distribution, with some Lyme-intense areas having high prevalence, and other areas having a low prevalence. Other infections, such as Lyme-associated Bartonella, Babesia, Ehrlichia and non-Lyme-associated CMV, Plasmodium species, Toxoplasma species and Treponema species may also be associated with ASD.6


Final comments to part 1

When neurological symptoms are present, infections of the CNS must be considered. Brain infections can stimulate glial responses, and the presence of viral and bacterial infections in nerve cells, can stimulate autoimmune responses against nerve cell antigens as well as the infections within them.155 For example, in MS some 20 different bacterial and viral infections have been found, but the link between these infections and the pathogenesis of MS is still being debated.16, 47, 75 One or even a few types of infections cannot be causally linked to MS, and the reason for this is that there may be too many possibilities. No one infection or a group of infections needs to be the trigger in MS to be important in the pathogenesis of MS. In time combinations of certain infections may eventually be identified at least in a subset of MS patients, and this will allow the development of new therapeutic approaches for many MS patients that are not recognized today.

One problem that is rarely discussed is the apparent disparity between the laboratory results from different laboratories. Often different laboratories cannot agree on types of infections found in various chronic diseases.47 There are a number of reasons for this, including differences in the source of materials, qualities of reagents and techniques used.16 Some procedures, such as PCR, have specific challenges that must be overcome in the handling of specimens, their stability, presence of interfering substances, contamination, sensitivity and specificity of the tests and interpretation of the results. Variability in results from different laboratories will remain a problem unless research groups work closely together to solve these problems. One example of how this has been overcome is a multi-centre research study on the presence of C. pneumoniae in the cerebrospinal fluid of clinically defined, mono-symptomatic MS patients.156 Sriram et al.156 conducted this diagnostic trial with good concordance of results between different laboratories. Cooperative studies such as this should eventually alleviate discrepancies in the types of infections found by different research groups.

This review continues in Part 2 with psychiatric diseases, autoimmune diseases, fatiguing illnesses, and other infectious diseases with neurological aspects and an overall discussion of the topic. 157



Competing Interests
None Declared
Author Details
GARTH L. NICOLSON, Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, California 92647, USA JORG HAIER, Department of General and Visceral Surgery, University Hospital, Münster 48149, Germany
CORRESSPONDENCE: Prof. Garth L. Nicolson, Office of the President, The Institute for Molecular Medicine, P.O. Box 9355, S. Laguna Beach, California, 92652 USA
Email: gnicolson@immed.org

References

1.Nicolson GL, Nasralla M, Haier J, et al. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med Sentinel1999; 4: 172-176.
jne

[soijuv]

Tutkimuksia borreliabakteerin osallisuudesta Alzheimerin tautiin. Viimeisenä suomalainen tutkimus jossa todettiin hermosolujen viestintäreitti, joka johtaa hermosolujen kuolemaan. Yhdessä potilaskertomuksessa tri A. McDonald löysi dementiaan kuolleen miehen aivoista borreliabakteereita. Yksi bakteereista oli juuri tunkeutumassa hermosolun sisälle. Kertomus löytyy osoitteesta

http://www.canlyme.com/jim_foris.html


1. Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.
Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 673-81.
PMID: 15665404 [PubMed - indexed for MEDLINE]

2: Kuntzer T, Bogousslavsky J, Miklossy J, Steck AJ, Janzer R, Regli F.
Borrelia rhombencephalomyelopathy.
Arch Neurol. 1991 Aug;48(8 ):832-6.
PMID: 1898257 [PubMed - indexed for MEDLINE]

3: Miklossy J, Kuntzer T, Bogousslavsky J, Regli F, Janzer RC. Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis.
Acta Neuropathol (Berl). 1990;80(5):568-72.
PMID: 2251916 [PubMed - indexed for MEDLINE]

4. Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer's disease.

Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H.
University Institute of Pathology, Division of Neuropathology, Lausanne, Switzerland.Neuroreport. 1994 Jun 2;5(10):1201-4.

Recently it was reported that, at autopsy, in neuropathologically confirmed cases of Alzheimer's disease spirochaetes were found in blood and cerebrospinal fluid using dark-field microscopy. Moreover, the spirochaetes were isolated and cultured from brain tissue. We now show, using scanning electron microscopy and atomic force microscopy that the helically shaped microorganisms isolated and cultured from the Alzheimer brains possess axial filaments. This indicates that these microorganisms taxonomically indeed belong to the order Spirochaetales. A morphometric analysis reinforces this notion.

PMID: 7919164 [PubMed - indexed for MEDLINE]


Medical News 8.3.2007 http://www.medicalnewstoday.com/youropi ... onid=14575

MacDonald in 1986 and 1987 and 1989 published evidence for Borrelia in Alzheimer's disease Autopsy tissue as follows:
1. Borrelia spirochetes present in Autopsy Alzheimer's disease tissue using Monoclonal murine antibodies to H5332 and H9724 epitopes of Borrelia burgdorferi.
2. Borrelia burgdorferi was isolated from in vitro cultures of Autopsy Alzheimer's Disease tissue - with immunoreactivity to Monoclonhal Antibody H5332, which is specific for B. burgdorferi.

Plaques of Alzheimer?s disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete

Alan B. MacDonald *

St. Catherine of Siena Medical Center, Department of Pathology, 50 Rte 25 A, Smithtown, NY 11787, USA

Received 20 February 2006; accepted 23 February 2006

http://www.e-clipx.ch/lyme/documents/Al ... _May_3.pdf

Summary Here is hypothesized a truly revolutionary notion that rounded cystic forms of Borrelia burgdorferi are the root cause of the rounded structures called plaques in the Alzheimer brain. Rounded ??plaques? in high density in brain tissue are emblematic of Alzheimer?s disease (AD). Plaques may be conceptualized as rounded ??pock mark-like?? areas of brain tissue injury. In this century, in brain tissue of AD, plaques are Amyloid Plaques according to the most up to date textbooks. In the last century, however, Dr. Alois Alzheimer did not require amyloid as the pathogenesis for either the disease or for the origin of its plaques. Surely, amyloid is an event in AD, but it may not be the primal cause of AD. Indeed in plaques, amyloid is regularly represented by the ??congophilic core?? structure which is so named because the waxy amyloid material binds the congo red stain and is congophilic. However an accepted subset of plaques in AD is devoid of a congophilic amyloid core region (these plaques ??cotton wool?? type plaques, lack a central congophilic core structure).

Furthermore, there is ??plaque diversity?? in Alzheimer?s; small, medium and large plaques parallel variable cystic diameters for Borrelia burgdorferi. Perturbations of AD plaque structure (i.e. young plaques devoid of a central core and older plaques with or without a central core structure) offer room for an alternate pathway for explanation of ontogeny of the plaque structures. If amyloid is not required to initiate all of the possible plaques in Alzheimer?s, is it
possible that amyloid just a by product of a more fundamental primal path to dementia? If a byproduct status is assigned to amyloid in the realm of plaque formation, then is amyloid also an epiphenomenon rather than a primary pathogenesis for Alzheimer?s disease. In the ??anatomy is destiny?? model, cysts of borrelia are always round. Why then not accept roundness as a fundamental ??structure determines function?? argument for the answer to the mystery of why Alzheimer plaques are always round? Parataxis causality, a concept borrowed from philosophy, is the error that comes from linking two events, which occur contemporaneously or in close proximity to one another with a cause and effect relationship.

Parataxis tells us that what appears to be cause and effect in the couplet ??amyloid plaque?? merely by a proximity relationship may be ??spurious causality?? which is a cognitive dead end.

_c 2006 Elsevier Ltd. All rights reserved.


Turun yliopiston tutkijat löysivät hermosolujen kuolemaan johtavan viestintäketjun

ANNE SAVOLAINEN

Turun yliopiston Biotekniikan keskuksen työryhmät ovat akatemiatutkija Michael Courtneyn ja dosentti Eleanor Coffeyn johdolla onnistuneet kuvaamaan molekyylitasolla uuden hermosolujen viestintäreitin, joka johtaa hermosolujen kuolemaan. Hermosolujen kuolemalla on tärkeä rooli aivojen rappeumasairauksissa, kuten Alzheimerin taudissa, epilepsiassa ja aivohalvauksessa.

- Solujen viestintäketjuja on tutkittu tarkkaan esimerkiksi syöpätutkimuksessa, mutta samankaltaisten viestiketjujen löytyminen hermosolujen yhteydessä oli suuri yllätys, Michael Courtney kertoo.

Tämä tarkoittaa sitä, että on olemassa runsaasti syöpäsolujen viestiketjuja koskevaa tutkimuskirjallisuutta, jota voidaan soveltaa hermosolujen viestiketjujen tutkimuksessa.

Monissa neurologisissa sairauksissa ja sairaskohtauksissa hermosolut aktivoituvat epätavallisen voimakkaasti, mikä johtaa hermosolujen kuolemaan. Rho-proteiinin, joka on jo pitkään yhdistetty syövän syntyyn, on nyt julkaistussa tutkimuksessa havaittu olevan tärkeässä roolissa myös hermosolujen tuhoutumisessa.


Lääkehoito vielä kaukana

Tutkimustulos tarjoaa mahdollisuuden kehittää lääke vakavien neurologisten sairauksien hoitoon.

- Lääketutkimuksessa ongelmaksi voi muodostua lääkkeiden sivuvaikutukset, mutta viestiketjun proteiinien tarkempi tutkimus edesauttaa oikeanlaisen lääkkeen kehittämistä, Eleanor Coffey pohtii.

Tutkimuksen kohteena oleva Rho-proteiini kuuluu proteiiniperheeseen, jonka jäsenten väliset viestiketjut liittyvät solujen tuhoutumiseen.

Tutkimuksessa osoitettiin, että Rho-proteiini aktivoituu solunsisäisen kalsiumin välityksellä, mikä johtaa solujen kuolemaan. Kun Rho-proteiinin aktiivisuus estetään geneettisen muokkaamisen avulla, solut pysyvät elossa.

- On olemassa erilaisia sairauksia, joissa hermosolujen viestintäreitin tutkimus on oleellista. Alzheimerin taudissa ongelmat ovat suurempia, ja ratkaisu ajallisesti kauempana. Esimerkiksi aivohalvaustapauksissa meillä on yhteistyökumppani, joka on tehnyt kliinisiä lääketestejä jo useiden vuosien ajan. Sillä saralla hoitoa voi löytyä vuosien päästä, Michael Courtney kertoo tutkimuksesta, jonka tuloksista tämän hetkiset potilaat eivät välttämättä vielä hyödy.

Tutkijat toivovat kuitenkin, että tutkimustulosta voidaan hyödyntää suunniteltaessa kohteita hermosolujen kuolemalta suojaaville lääkeaineille.

TS 20.3.2007

[soijuv]

http://m.iltalehti.fi/terveys/2016053121652944_tr.shtml

Bakteerit esim borrelia bakteeri ja erilaiset virukset esim herpes virukset Alzheimerin taudin oireiden aiheuttajia.

[Jatta1001]

https://neurosciencenews.com/microbes-a ... logy-3826/
Konekäännös

Abstrakti

Mikrobit ja Alzheimerin tauti

Olemme tutkijoita ja lääkäreitä, jotka työskentelevät Alzheimerin taudin (AD) tai siihen liittyvien aiheiden parissa, ja kirjoitamme ilmaistaksemme huolemme siitä, että yksi erityinen taudin näkökohta on laiminlyöty, vaikka siihen perustuva hoito saattaa hidastaa tai pysäyttää AD: n etenemisen. Viitaamme moniin tutkimuksiin, jotka koskevat pääasiassa ihmisiä, ja jotka vaikuttavat erityisiin mikrobiin vanhusten aivoissa, etenkin tyypin 1 herpes simplex-virusvirukseen (HSV1), Chlamydia pneumoniae -lajeihin ja moniin spirocateen tyyppeihin AD: n etiologiassa. AD-aivojen [5, 6] sieni-infektio on myös kuvattu, samoin kuin epänormaali mikrobiota AD-potilaan veressä. Ensimmäiset HSV1-havainnot AD-aivoissa raportoitiin melkein kolme vuosikymmentä sitten]. Näiden tutkimusten jatkuvasti kasvava määrä (nyt noin 100 pelkästään HSV1: llä) edellyttää infektion ja AD-käsitteen uudelleenarviointia.

AD: hen liittyy hermostokato ja progressiivinen synaptinen toimintahäiriö, johon liittyy amyloidi-β (Aβ) -peptidin, amyloidi-β -proteiinin prekursorin (AβPP) pilkkotuotteen ja tau-proteiinin epänormaalien muotojen muodostuminen, merkit, joita on käytetty taudin diagnostisina perusteina. Ne ovat AD: n tunnusmerkkejä, mutta ovatko ne AD: n syitä tai seurauksia, ei tiedetä. Ehdotamme, että nämä ovat tarttuvan etiologian indikaattoreita. AD-tapauksissa ei usein ymmärretä, että mikrobit voivat aiheuttaa sekä kroonisia että akuuteja sairauksia; että jotkut mikrobit voivat pysyä piilevänä kehossa mahdollisena uudelleenaktivoitumisena, jonka vaikutukset voivat ilmetä vuosia alkuperäisen tartunnan jälkeen; ja että ihmiset voivat olla tartunnan saaneita, mutta eivät välttämättä vaurioituneita siten, että 'kontrollit' ovat jopa oireettomia, vaikka ne olisivatkin saaneet tartunnan

“Mikrobit ja Alzheimerin tauti”, kirjoittanut Itzhaki, Ruth F .; Sorvi, Richard; Balin, Brian J .; Ball, Melvyn J .; Kantaja, Elaine L .; Bullido, Maria J .; Carter, Chris; Clerici, Mario; Cosby, S. Louise; Kenttä, Hugh; Fulop, Tamas; Grassi, Claudio; Griffin, W. Sue T .; Haas, Jürgen; Hudson, Alan P .; Kamer, Angela R .; Kell, Douglas B .; Licastro, Federico; Letenneur, Luc; Lövheim, Hugo; Mancuso, Roberta; Miklossy, Judith; Lagunas, Carola Otth; Palamara, Anna Teresa; Perry, George; Preston, Christopher; Pretorius, Etheresia; Strandberg, Timo; Tabetti, Naji; Taylor-Robinson, Simon D.; ja Whittum-Hudson, Judith A., Journal of Alzheimer Disease . Julkaistu verkossa 8. maaliskuuta 2016 doi: 10.3233 / JAD-160152

[Jatta1001]

https://content.iospress.com/articles/j ... igjrUVPGoM

Borrelia burgdorferi lokalisoituu yhdessä amyloidimarkkerien kanssa Alzheimerin taudin aivokudoksissa
Artikkelin tyyppi: Tutkimusartikkeli Hyväksytty 24.10.2021 | Julkaistu: 05.12.2021

Tekijät: Senejani, Alireza G. a ; * | Maghsoudlou, Jasmin ja | El-Zohiry, Dina a | Gaur, Gauri a | Wawrzeniak, Keith a | Caravaglia, Cristina a | Khatri, Vishwa A. a | MacDonald, Alan b | Sapi, Eva a
Liitteet: [ a ] Biologian ja ympäristötieteiden laitos, New Havenin yliopisto, West Haven, CT, USA | [ b ] Molecular Interrogation Research Laboratory, Napoli, FL, USA
Kirjeenvaihto: [*] Kirjeenvaihto: Alireza G. Senejani, Biologian ja ympäristötieteiden laitos, New Havenin yliopisto, 300 Boston Post Road, West Haven, CT, 06516, USA. Sähköposti: asenejani@newhaven.edu .

Tiivistelmä: Taustaa: Bakteeri- tai virusperäisten infektioiden on oletettu vaikuttavan neurodegeneratiivisten sairauksien etiologiaan.
Tavoite: Tässä tutkimuksessa tarkasteltiin Borrelia burgdorferi spirokeetin, Lymen taudin aiheuttajan, mahdollista esiintymistä potilaiden aivojen ruumiinavauskudoksessa.joilla on joko Alzheimerin (AD) tai Parkinsonin tauti. Menetelmät: Potilaiden aivokudosleikkeistä, joilla oli saman ikäisiä kontrolleja, arvioitiin B. burgdorferin antigeenin ja DNA:n läsnäolo eri menetelmillä. Positiiviset Borrelia-rakenteet arvioitiin rinnakkaispaikallistumisen suhteen biofilmin ja AD-markkerien, kuten amyloidin ja fosfo-taun (p-Tau), kanssa käyttämällä immunohistokemiallisia menetelmiä.
Tulokset: Tulokset osoittivat B. burgdorferi -antigeenin ja DNA:n esiintymisen potilailla, joilla oli AD-patologia, ja heistä yhdellä oli aiemmin diagnosoitu Lymen tauti. Mielenkiintoista on, että spiroketaalirakenteiden ohella löydettiin merkittävä määrä Borrelia-positiivisia aggregaatteja, joissa on tunnettu biofilmimerkki, alginaatti. Immunohistokemialliset tietomme osoittivat myös, että Borrelia-positiiviset aggregaatit lokalisoituivat yhdessä amyloidi- ja anti-fosfo-tau-markkerien kanssa. Osoittaaksemme edelleen B. burgdorferin ja amyloidien mahdollisen suhteen, infektoimme kaksi nisäkässolulinjaa B. burgdorferilla, mikä johti amyloidi-β- ja p-Tau-proteiinien ilmentymisen merkittävään lisääntymiseen molemmissa solulinjoissa infektion jälkeen.
Johtopäätös: Nämä tulokset osoittavat, että B. burgdorferi voidaan löytää AD-aivokudoksissa, ei vain spirokeetoissa, vaan tunnetussa antibiooteille vastustuskykyisessä biofilmimuodossa ja sen paikallisissa amyloidimarkkereissa.
Yhteenvetona tämä tutkimus tarjoaa todisteita todennäköisestä yhteydestä B. burgdorferi -infektioiden ja biofilmin muodostumisen, AD-patologian ja kroonisten hermostoa rappeuttavien sairauksien välillä. burgdorferi, mikä johti merkittävään lisääntymiseen amyloidi-β- ja p-Tau-proteiinien ilmentymisessä molemmissa solulinjoissa infektion jälkeen.

Avainsanat: Alzheimerin tauti, amyloidi, biofilmi, Lymen neuroborrelioosi, tau-proteiinit
DOI: 10.3233/JAD-215398
Journal: Journal of Alzheimer's Disease , voi. Prepress, ei. Pre-press, s. 1-15, 2021
Hyväksytty 24.10.2021 | Julkaistu: 05.12.2021