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.

Aging-related immunosenescence can increase susceptibility to pathogens due to immunodeficiency, but it is also accompanied by an increase in the pro-inflammatory activity of monocytes and macrophages which can lead to chronic low grade inflammation, termed "inflamm-aging" [31, 32] . This increased inflammatory function also applies to microglia [194] . Certain AD gene variants are associated with enhanced pro-inflammatory responses (see above) and cerebral pathogen entry would thus be met with a doubly vigorous inflammatory response related to both immunosenescence and genetic variation. Persistently activated monocyte/macrophages have been observed in the blood of patients with early AD [195] and increased activation of microglia/macrophages, colocalized with the area of heavy A␤ concentration, is also observed in the brains of AD patients [196] .