Actually, APOE ε4 was first identified and shown to be associated with the increased risk of AD in late-onset FAD, and then association studies in cohorts identified it as a major genetic risk factor for late-onset SAD (Pericak-Vance et al. 1991; Corder et al. 1993; Strittmatter et al. 1993). Here, APOE is linked to familial Alzheimer disease.