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.

While there are statistical limitations to this type of analysis, correction for false discovery followed by the Bonferroni correction has been conservatively applied. The relationship of AD to pathogens is supported by experimental observation and by the antimicrobial effects of A␤. This study also relies on multiple and diverse in silico bioinformatic analyses linking AD GWAS genes, plaques and tangles as well as the hippocampal transcriptome to multiple pathogen interactomes, and the upregulated AD hippocampal genes to multiple infection datasets from diverse pathogen species. Polymicrobial involvement is also supported by the diversity of bacterial, viral and fungal sensors and defenders that are upregulated in the AD brain, blood, or CSF. Each comparison relates to single pathogens but given the diversity of pathogens detected in AD such effects are likely to be cumulative.