APOE and Alzheimer disease: The three APOE gene variants APOE2 (cystine 112, cystine 158), APOE3 (cystine 112, arginine 158), and APOE4 (arginine 112, arginine 158) have differing effects on AD risk: while the APOE4 allele raises risk, the APOE2 allele is considered protective, and the APOE3 allele is neutral (Husain et al. 2021; Roses 1996).