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

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.

A Rabbit Model of Acanthamoeba Keratitis That Better Reflects the Natural Human Infection

“…Both models (conventional and novel) were successfully established in the present study, and were shown to satisfy the Koch's criteria (Miklossy, 2011) for a causative relationship between a microbe and a disease: (1) The Acanthamoeba trophozoites or cysts were found either on the surface of the infected cornea or on the histochemical sections of infected corneas; (2) the clinical manifestations of typical keratitis caused by A. healyi infection were observed, including edema, opaque cornea, ulceration, abscess, and congestion; (3) the typical pathological features of keratitis were observed in the infected corneas, including inflammatory cells infiltration, neovascularization, and fibrosis; and (4) a strong immune response was observed with high antiAcanthamoeba IgG antibody titers, and elevated levels of total IgG, IgM, and INF-g in the sera of infected rabbits.…”

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

“…For this reason, we established a homemade indirect ELISA to measure the RL levels in CSF. The CSF samples of AD patients (21), MCI patients (13), and controls (7) were used. The CSF samples were taken from different individuals than those who provided the serum samples.…”

“…The surviving cells are able to expel strongly inflammatory components including LPSs [16]. The imputed role of pathogens in AD has been extensively reported for about over 200 different helical bacterial spirochete species [17], which may co-infect with other Gram-negative phylotypes [18][19][20][21][22][23][24][25][26][27][28][29].…”

Lyme Disease Bacterium, Borrelia burgdorferi Sensu Lato, Detected in Multiple Tick Species at Kenora, Ontario, Canada

“…Other researchers have cultured and detected B. burgdorferi s.l. in the brains of psychiatric and Alzheimer's disease patients at autopsy [62][63][64][65][66][67]. Persistence of B. burgdorferi s.l.…”