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 tissue and cellular distribution of the 78 AD genes were analyzed using the functional enrichment analysis tool (FUNRICH) [100] (http://funrich.org/index.html) which derives proteomic and genomic distribution data from >1.5 million annotations. It provides the total number of genes in datasets from each region sampled and returns the significance of any enrichment for the uploaded AD genes, using the hypergeometric probability test, with p values corrected using the Storey and Tibshirani method (Q values) [100] . AD gene enrichment was also analyzed in a BBB proteome dataset of mouse cerebral arteries (6620 proteins) [101] . The presence of the AD genes in exosomes, a means of transit through cells allowing intercellular communication [102, 103] , was assessed using Exo-Carta (http://www.exocarta.org) a manually curated database of exosomal proteins, RNA and lipids [104] . The exosomal pathway is hijacked by several viruses, contributing to intercellular spread and immune evasion [105, 106] .