APOE and Alzheimer disease: Despite more than three decades of evidence supporting the dominant role of APOE4 and APOE2 genetics, the enrichment of ApoE protein in hallmark lesions, and extensive lipid peroxidation in AD brains, specific molecular feature(s) and unambiguous feature-dependent mechanism(s) directly linking Cys→Arg exchanges in ApoE to AD risk have not been clearly defined.