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.

To this end, the pathogen specificity of these sensors and defenders was reviewed, generally and in relation to the pathogens in this study. These properties were then matched to reported expression changes in the AD brain, blood, or CSF in relation to the pathogens in this study and to others. This analysis is reported in Supplementary Table 2, which shows that the expression changes seen in AD relate to sensors and defenders for the diverse pathogens, and to many other viruses, bacteria, or fungi. They are not restricted to viral, fungal, or bacterial defense, supporting a polymicrobial involvement. 99 antimicrobial/pattern recognition, antiviral and related defensive genes were identified that were upregulated in the AD brain, blood, or CSF. No single pathogen or group of pathogens (bacteria, viruses, or fungi) accounted for all of these changes. In terms of the pathogens related to this study, influenza, C. albicans, and HSV-1 matched the highest number of AD-affected genes, but high scores were also obtained for other bacteria (including Enterococci, E. coli, streptococci, staphylococci, pseudomonas, listeria), fungi (including Aspergillus and Saccharomyces species), or viruses (e.g., Sendai virus, coxsackie B virus, coronaviruses, and flaviviruses (dengue virus and West Nile virus) (Supplementary Table 2 : Fig. 7A) .