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.

In summary, BBB disruption is promoted by aging and can also be influenced by viral infection via the nasal route, which attains the brain regions first affected in AD. Other bacterial and fungal pathogens also have different ways of circumventing or damaging the BBB. Aging related immunosenescence and autoimmune blockade of the antimicrobial effects of A␤ would contribute to pathogen survival in the periphery. Nasal immunosenescence occurs at a later stage [179] , thus limiting the naso-cerebral route to the elderly. The pro-inflammatory gain of function provided by immunosenescence and by certain AD gene variants suggests that cerebral pathogen entry in the aged would be met by a vigorous proinflammatory response that likely plays a major role in the degenerative process.