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 environmental risk factors associated with AD disrupt the BBB, and BBB integrity is maintained by the beneficial factors (Table 1) . While infections are random uncontrollable events, many of the other environmental risk factors are modifiable by lifestyle changes, for example diet, obesity, smoking, and exercise, and it has been estimated that addressing such modifiable risk factors could result in a significant reduction in the incidence of AD [206] . Interestingly, some of these beneficial factors also possess antimicrobial effects, suggesting a multifactorial action. For example, statins have broad spectrum antimicrobial effects (certain oral bacteria as well as viruses and fungi) [243] , while NSAIDs have antibacterial effects related to an ability to inhibit bacterial DNA replication [244] . Melatonin also has antimicrobial effects against bacteria and viruses [245] and memantine also has antiviral effects against a neurotropic strain (HCoV-OC43) of a human respiratory coronavirus [246] as well as the influenza or HIV-1 viruses [247, 248] .