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.

There have been few studies attempting to relate specific AD genes to pathogen resistance. The APOE4 allele is geographically concentrated in tropical regions with a high parasite burden [69] and may also contribute to resistance against Giardia and cryptosporidial diarrhoeal infections in young children [70, 71] . The frequency of this allele is high in sub-Saharan Africa and other areas where malaria is endemic, but while plasma samples from APOE4 subjects inhibit the growth of the malaria parasite Plasmodium falciparum [72] , APOE alleles had no major protective effects against malaria in Gambian children [73] . APOE2 has been reported as a potential risk factor for early malaria infection in Ghanaian infants [74] . APOE4 possession may also have a protective effect against hepatitis C infection and enhances viral clearance in infected patients [75] . Old age is the principal risk factor in AD, and this too implies survival from the many infectious diseases that have been and in many regions still are among the greatest causes of death in children and adults [76, 77] .