The APOE4 variant of apolipoprotein E was identified 30 years ago as the major genetic risk factor for Alzheimer’s Disease (AD) at the population level (Bennett et al, 2009; Corder et al, 1993; Strittmatter et al, 1993) while the APOE2 variant was the first identified protective allele against AD (Corder et al, 1994; Nagy et al, 1995). The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.