Finally, current top hits associated with AD, including the bridging integrator 1 (BIN1) [13], clusterin (CLU) [14], [15], the ATP-binding cassette sub-family A member 7 (ABCA7) [16], the complement component (3b/4b) receptor 1 (CR1) [15], and the phosphatidylinositol binding clathrin assembly protein (PICALM) [14], do not account for the entire genetic contribution of the disease or surpass the risk conferred solely by the APOE-ε4 allele. The gene discussed is APOE; the disease is Alzheimer disease.