APOE and Alzheimer disease: There are three principal alleles at the apolipoprotein E locus, APOE (19q13.2): ε2 (cys112, cys158), ε3 (cys112, arg158), and ε4 (arg112, arg158), giving six different genotypes in human populations, with some further minor variants (reviewed in [47-49]); homozygosity for ε4 is the greatest risk factor for both AD and ATH, with risk ratios declining generally ε4 > ε3 > ε2.