APOE and Alzheimer disease: We examine four major forms of AD genetic risk: (1) APOE-ε4, the strongest known genetic factor for LOAD, which is also associated with early-onset AD [20], (2) APOE-ε2, a protective allele of AD, (3) Polygenic risk, using the AD PRS (with APOE excluded) as a proxy, and (4) Familial risk, according to the parental history of AD.