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 hippocampal genes upregulated in AD were significantly enriched in upregulated genes in datasets from multiple viral species and responses to double stranded RNA or to the double-stranded RNA viral mimic/TLR3 agonist, Polyinosinic:polycytidylic acid (poly I:C) (Fig. 5) . The viruses ranged from the benign (e.g., the rhinovirus that causes the common cold) to the highly malignant (e.g., the ebolavirus, rabies virus or HIV-1). They include common human infectious agents (e.g., adenovirus 5, influenza, EBV, HSV-1, measles or the Norwalk virus). Apart from HSV-1, the human cytomegalovirus, HIV-1, or hepatitis C, none of these have been implicated in AD or dementia. No infection-related datasets were found for microglia, the brain resident immunocompetent cells, but significant enrichment of the AD upregulated genes was observed for genes upregulated by interferon gamma in microglial cells (Fig. 5) . Interferon gamma plays an important role in the response to viral, bacterial, and parasitic infections [149] .