Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer's disease

Abstract

The purpose of this investigation was to use molecular and immunological techniques to determine whether oral Treponema infected the human brain. Pieces of frontal lobe cortex from 34 subjects were analyzed with species-specific PCR and monoclonal antibodies. PCR detected Treponema in 14/16 Alzheimer's disease (AD) and 4/18 non-AD donors (P < 0.001), and AD specimens had more Treponema species than controls (P < 0.001). PCR also detected Treponema in trigeminal ganglia from three AD and two control donors. Cortex from 15/16 AD subjects and 6/18 controls contained Treponema pectinovorum and/or Treponema socranskii species-specific antigens (P < 0.01). T. pectinovorum and/or T. socranskii antigens were also found in trigeminal ganglia and pons from four embalmed cadavers, and 2/4 cadavers also had Treponema in the hippocampus. These findings suggest that oral Treponema may infect the brain via branches of the trigeminal nerve.

Alzheimer's Disease and Peripheral Infections: The Possible Contribution from Periodontal Infections, Model and Hypothesis

“…In addition, B. burgdorferi specific antigens were co-localized with Aβ deposits and glial and neuronal cells exposed to B. burgdorferi were able to produce amyloid beta precursor protein and hyperphosphorylated tau proteins [81], suggesting that B. burgdorferi is able to induce AD specific pathology. Of interest, spirochetes from the oral cavity have been reported by Riviere in brain samples from AD patients were using molecular and immunological methods [101]. These results suggest, as did Miklossy's results that spirochetes within brain tissue may originate from diverse areas including the oral cavity [78].…”

“…For example, Treponema species including T. denticola were detected in 14/16 AD and 4/18 non-AD brains. In addition, AD specimens also had more Treponema species than controls [101]. In an animal model of oral infections T. denticola was detected postmortem in the brain [30].…”

Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes

“…Recent biochemical, biophysical, and imaging analyses revealed that fibers produced by E. coli, termed "curly" were composed of amyloid [5]. It was suggested that several types of spirochetes may be involved in AD, and also that amyloidogenic proteins may be an integral part of spirochetes, which may, therefore, play a role in amyloidogenesis in AD [18][19][20][21][22][23][24][25]31]. Furthermore, it was shown that the OspA outer surface protein of B. burgdorferi forms amyloid fibrils in vitro, similar to human amyloid [26].…”

Periodontal Disease as a Possible Risk Factor for Alzheimer’s Disease

“…Accordingly, it is known to cause a strong inflammatory response. In addition, the interesting finding is that a periodontal disease-related bacteria of the Treponema genus was found in the trigeminal ganglion, brainstem, and cerebral cortex; its frequency is said to be high in patients with AD in particular [6]. This finding suggests that periodontal disease-related bacteria can be directly transmitted into the brain and cause inflammation.…”

“…To date, periodontal disease has been reported as a risk factor for diabetes mellitus (DM), cardio-and cerebrovascular disease, aspiration pneumonia, premature and low birth weight infants, bacterial endocarditis, glomerulonephritis, arthritis, and palmoplantar pustulosis [1][2][3][4][5]. The following three pathways are assumed to be the mechanism of the systemic spread of periodontal disease: direct action of bacterial body and toxin of periodontal disease-related bacteria at the local periodontal site that spread to target organs through the hematogenous route or respiratory tract [4]; the action of inflammation-inducing substances such as cytokines, which are produced by the inflammatory response within periodontal tissue or immune response that spread hematogenously to the target organs [5]; and a pathway that results in intracerebral spread through the nervous system [6,7]. There are various data on intravascular infiltration of periodontal disease-related bacteria and its spread to target organs thus far, but its mechanism of affecting diseases is not fully understood.…”