APOE and Alzheimer disease: It remains to be shown whether the differential effects of APOE variants on the risk of Alzheimer’s dementia are related to their recognized effects on Aβ oligomerization5–7, morphology, or clearance, their suggested effects on TREM2-mediated microglial response, tau pathology, LDLR binding, HSPG binding, mitochondrial function, neurodegeneration, a non-additive protective effect of APOE2 in reducing the expression of a microglial aging signature (HuMi Aged geneset)17, or a combination of these and other effects5,7,18–23.