APOE and Alzheimer disease: Here, we propose the overarching hypothesis that the super-ability (for ApoE2), intermediate ability (for ApoE3) or complete inability (for ApoE4) to form disulfide bridge-linked ApoE multimers or dimers is the central molecular determinant accounting for the disparate effects of APOE2, APOE3 and APOE4 alleles on Aβ and pTau pathology and AD risk in humans.