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.

AD genes are also enriched in the lateral ventricle, a site of the choroid plexus [119] . This provides CSF and is the location of the blood-CSF barrier, which is exploited by pathogens to gain access to the brain. The choroid plexus plays an important role in pathogen defense [120] . Postmortem gene expression studies of the choroid plexus epithelium in AD patients show changes indicative of increased permeability of the blood-CSF barrier and a reduction of macrophage recruitment [121] , factors that would favor pathogen entry and reduce their phagocytosis by macrophages. The hippocampus bulges into the temporal horn of the lateral ventricle [122] and this area, a keystone of AD pathology, is thus in close proximity to a major site of cerebral pathogen entry. AD genes are also enriched in a separate BBB dataset from mouse cerebral arteries. This is discussed in greater detail below. Other barriers in intestinal and pulmonary tissues, also enriched in AD genes ( Fig. 1) , might also be considered as potential sites of pathogen entry. Immune systems play an important role at barrier interfaces [123] .