Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90
Published: 4 August 2011
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.
These are my preliminary comments, I may come back at some point to revise them.
This paper is one in a long line of research by Dr. Miklossy on the relationship between infection and Alzheimer's disease, with a much earlier similar work being "Alzheimer's disease - a spirochetosis?"
Those of you who were interested in reading the paper on which this abstract was based may also find the following full text of interest:
The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Stephanie J. Soscia, James E. Kirby, Kevin J. Washicosky, Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A. Burton, Lee E. Goldstein, Scott Duong, Rudolph E. Tanzi, Robert D. Moir.
Source link: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009505
And there are examples of other papers not by Dr. Miklossy in a similar vein which may be of interest:
I realize that a number of Lyme disease patients - especially those with persisting neurological symptoms - are probably reading the abstract and feeling somewhat nervous about their future potential for developing Alzheimer's disease. However, I want to point out a few pieces of information from the paper itself which highlight two important items:
1) That we don't know exactly what causes Alzheimer's disease yet and
2) That in the samples studied, the majority of Alzheimer patients' brains of those sampled which were infected did not contain Borrelia burgdorferi spirochetes.
Before everyone reading along rests easy, though, you might want to take note that the analysis states that in those samples studied, there is a strong statistical correlation with the presence of other spirochetal bacteria in the brains of patients with Alzheimer's disease.
|Graph showing that Alzheimer disease patient|
samples contained more oral spirochetes and B.
burgdorferi compared to control groups.
Yet while many are infected with such virus, most people do not go on to develop Alzheimer's disease. Why is that? Is one specific kind of pathogen the precursor that leads to beta amyloid plaques?
This said, spirochetes - especially periodontal ones, but also Borrelia burgdorferi - may play a role in the development of Alzheimer's disease.
Miklossy states in her paper:
"When considering all studies (Table 1, Fig. 1) detecting all types of spirochetes and their specific species, their frequency was 8 times higher in the brain in AD (90/131= 68.7%) compared to controls (6/71 = 8.45 %).The difference is statistically significant (P = 1.7 x 10-17; OR = 23; 95% CI = 9-71, N = 202). The association remains strongly significant when the 12 cases with mild AD-type changes (P = 1.5 x 10-19, OR = 26, 95% CI = 10-80, N = 214) or those cases where spirochetes were analyzed in the blood were also included (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247)."
Those are some crazy P values.
I am still looking at those studies which are referred to in Table 1, Figure 1 of Miklossy's recent paper: of the Bb studies, 3 are small scale studies by MacDonald, some by Miklossy, and then a few by others. I think more sample studies would be good... I also want to read up on their methods more.
It should be noted that 8 out of 10 of the spirochetal studies in the top half of the table are by Miklossy, and only 2 by McLaughlin. And there is only one specific periodontal spirochetal study mentioned by Riviere et al, 2002... Is anyone else doing research in this area?
But I digress...
Once Miklossy outlined the statistical analysis of the studies and the correlation between the presence of pathogens in the brain and Alzheimer's disease, she continued with an outline of how the pathogenesis of spirochetal infection leads to the development of specific immunological responses and reactions within the brain. This part is the most difficult to summarize, but the intention is to show how similar the unfolding pathogenesis of spirochetal brain infections is to the development of Alzheimer's disease.
Later on, Miklossy shows how to apply Koch's Postulates and Hill's Postulates to the studies conducted, though there isn't a full cycle of re-infection or true xenodiagnosis done from the samples extracted. This is something I would like to see in a new study.
The notable part of the conclusion, for me, is this part:
"Spirochetes are able to escape destruction by the host immune reactions and establish chronic infection and sustained inflammation. In vivo studies with long exposure times will be necessary to efficiently study the sequence of events and the cellular mechanisms involved in spirochete induced AD-type host reactions and Aβ-plaque, “tangle” and “granulovacuolar” formation. The characterization of all types of spirochetes and co-infecting bacteria and viruses is needed, in order to develop serological tests for the early detection of infection. The pathological process is thought to begin long before the diagnosis of dementia is made therefore, an appropriate targeted treatment should start early in order to prevent dementia."The basic message to take from this paper if you are a Lyme disease patient is that last sentence there:
"The pathological process is thought to begin long before the diagnosis of dementia is made. Therefore, an appropriate targeted treatment should start early in order to prevent dementia."
Regardless of the significance of the findings, early diagnosis and treatment of tickborne infections is paramount to reduce the risk of future problems. Something we all already knew.
My general thought about this meta-analysis is that more studies are needed and a larger collection of samples taken from Alzheimer disease patients need to be analyzed using similar means and methods. I think there is more that needs to be known about the relationship between any pathogenic invasion and the development of Alzheimer's disease.
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