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It has been reported previously that spirochetes could be one of the causes of Alzheimer's disease (AD). In this study, we have attempted to reproduce these findings by examining fresh blood samples from 22 patients diagnosed with early stage (n = 16) and late stage (n = 6) AD. The patients were participants in a clinical drug trial. Fresh necropsy brain cortical specimens from AD patients (n = 7) were also examined. Spirochetes were observed microscopically in the blood of only one late-stage AD patient. None of the brain tissues showed the presence of spirochetes. Our results suggest that spirochetes are probably not associated with AD.

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.

The aetiology of Alzheimer's disease (AD), which affects a large proportion of the aged population is unknown and the treatment unresolved. The role of beta amyloid protein (beta A4), derived from a larger amyloid precursor protein (APP) in AD is the subject of intense research. Here I report observations that in 14 autopsy cases with histopathologically confirmed AD, spirochetes were found in blood and cerebrospinal fluid and, moreover, could be isolated from brain tissue. Thirteen age-matched control cases were without spirochetes. Reference strains of spirochetes and those isolated from brains of AD patients, showed positive immunoreaction with monoclonal antibody against the beta amyloid precursor protein. These observations suggest that spirochetes may be one of the causes of AD and that they may be the source of the beta amyloid deposited in the AD brain.

Filamentous, fibronectin-immunopositive structures, previously described in Alzheimer's disease and control brains were negative for neuronal, glial, and macrophage markers. The present study sought to determine the nature of these entities and to further characterize their morphology, immunoreactivity and distribution between neuropathologies. Ultrastructural analysis shows these formations to be filamentous micro-organisms, which may belong to the actinomycetes. Immunohistochemistry for the cell-stress protein ubiquitin is consistently positive in these organisms. They are also present in Down's syndrome, dementia pugilistica, amyotrophic lateral sclerosis with dementia, and Parkinson's disease. The pattern of tissue distribution implies a pre-mortem invasion of the brain, and, as the micro-organism is present at a four to five-fold higher frequency in Alzheimer's disease, it may act pathogenically in this dementing illness.