APOE and Alzheimer disease: The mean age and frequency of AD at clinical onset in ε4 homozygotes are 68 years and 91%, respectively, 76 years of age and 47% in ε4 heterozygotes, and 84 years and 20% in ε4 noncarriers (Corder et al., 1993; Liu et al., 2013b; Rebeck et al., 1993), indicating that APOE4 leads to a dramatically increased risk of AD and lowers the age of disease onset in a gene-dose-dependent manner (Huang and Mucke, 2012).