6.12. ALZHEIMER'S DISEASE - A SPIROCHETOSIS.
Based on our observations we proposed that several types of spirochetes may be involved in AD, including e.g. oral, intestinal and Borrelia spirochetes (Miklossy 1993, 1994, 1996, Miklossy et al., 1994, 1996).
Antibodies to various types of oral spirochetes are highly prevalent in the population at large and it is important to consider that spirochetes of the oral cavity as well as intestinal spirochetes could contain amyloidogenic proteins and may induce chronic inflammation and amyloid deposition in the brain in analogy to Treponema pallidum and Borrelia burgdorferi. For the majority of these spirochetes, diagnostic and serological tests are not available. In our initial analysis of the potential involvement of spirochetes in AD, we have used well established techniques which can detect all types of spirochetes. We visualized by dark field microscopy helically shaped microorganisms in the CSF, blood and cerebral cortex in 14 AD cases that were absent in 13 controls (Miklossy 1993, 1994). We cultivated spirochetes from four of the 14 cases using BSK II medium. Three of them were available for further characterization. We have stressed that several types of spirochetes may be involved in AD and that characterization of the spirochetes isolated and cultivated from the brains of AD patients is needed (Miklossy, 1993).
Alan MacDonald was who first reported two cases of concurrent neocortical neuroborreliosis and AD (McDonald and Miranda, 1987; McDonald, 1988), where immunostaining showed Borrelia burgdorferi in brain tissue and the spirochetes were cultivated from the cerebral cortex in BSK medium.
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.
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.