APOE and Alzheimer disease: The present hypothesis—which attempts to fill that gap by proposing an unambiguous explanation for the isoform-dependent effects of APOE on lipoprotein peroxidation and AD risk—is integrated into our unifying model wherein peroxidation of ApoE-containing lipoproteins and consequent ApoE receptor-ligand disruption are the initiating molecular events that ultimately lead to AD in humans.[15, 16] This combined hypothesis is attractive because it provides a plausible, unambiguous molecular mechanism that: