Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

Carter, Chris J.

The relationship between pathogens and AD has a long history coupled with a degree of skepticism, perhaps related to an inability to fulfil Koch's postulate. For example, the same pathogen is not always found in all AD brains, or in different laboratories, and independent confirmation is required for several species of pathogen. Laboratory confirmation in animal models may be impossible for certain pathogens, for example the EBV or hepatitis C virus, that do not infect rodents. Nevertheless, the diversity of pathogens able to promote neurodegeneration, A␤ deposition or to mimic the effects observed in the hippocampal AD transcriptome suggests that many candidates, alone or severally, could be involved in the pathogenesis of AD. A polymicrobial involvement seems likely given the multiple species detected in the AD brain. Evidently, this could be assessed by microbiome studies in the periphery or in postmortem brains.