APOE and Alzheimer disease: Human APOE allele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer’s disease (AD); however, the specific molecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown.