APOE and Alzheimer disease: While APOE-e4 has been linked to a 2- to 3-fold increased risk of AD in heterozygotes (i.e., e2/e4 or e3/e4 genotypes) and 10 times the risk in homozygotes (ε4/ε4), compared to carriers of the most common APOE genotype, homozygotes of e3 (ε3/ε3) (Corder et al., 1993; Spira et al., 2017).