APOE and Alzheimer disease: Inheritance of the APOE ε4 allele (APOE4) is the strongest risk factor for AD, besides age, with one copy of APOE4 leading to a three-fold increased risk of AD and two copies leading to a 15-fold increased risk of AD (Corder et al., 1993; Strittmatter et al., 1993; Strittmatter and Roses, 1995).