APOE and Alzheimer disease: The above-mentioned association between APOE alleles and susceptibility to AD (APOE4 > 3 > 2) is mediated via multiple pathways: increased Aβ deposition and tau aggregation, induction of neuroinflammation through the production of proinflammatory cytokines and microglia stimulation, increased intracellular lipid accumulation, and disruption of effective myelin formation (among others) [45].