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.

This analysis is based on overlapping gene symbols rather than on specific polymorphisms. There is thus no indication of the physiological weight or importance of any gene/pathogen interaction, some of which will be more important than others. Pathogen effects may also be strain-dependent, and the size of the interactomes also varies widely. Within any large interactome there will be deleterious, neutral and beneficial effects. While HSV-1 infection causes A␤ deposition and neurodegeneration [251] , in its latent form, the virus can have neuroprotective effects. For example the viral latency transcript inhibits apoptosis and promotes neurite sprouting in neuroblastoma cells [252] , protects neuronal C1300 and Neuro2A cells from granzyme B-induced apoptosis and CD8 T-Cell killing [253] and also protects trigeminal neurons from apoptosis [254] . The Bornavirus is capable of promoting hippocampal degeneration in Man [11] . In rats Borna virus infection decreases choline acetyltransferase activity in the cerebral cortex, horizontal diagonal band of Broca, hippocampus and amygdala [255] a situation similar to that observed in AD [256] but the inflammation and microglial activation it produces can also reduce A␤ immunoreactivity in the brain parenchyma of Tg2576 mutant A␤ mice [13] . In adult mice, 12 months after infection, T. Gondii causes neurologic and behavioral abnormalities that are secondary to inflammation and neuronal loss. Activated microglia were also seen in perivascular areas and the brain parenchyma [257] . T. gondii infection in BALB/C mice also induces neuroinflammation and learning and memory deficits. It also potentiates the toxic effects of low doses of intracerebrally administered A␤ [258] , but chronic infection can also increase A␤ phagocytosis and clearance by recruited monocytes [259] .