We therefore propose that the absence of Cys, and resulting inability to form intermolecular disulfide bridges (Fig 2C), make ApoE4-containing lipoproteins uniquely vulnerable to peroxidation (Fig 2D–F) and ensuing peroxidation-induced pathological events, including the aldehydic adduction of Lys and His residues within the receptor binding motif of ApoE and crosslinking of ApoE with ApoE receptors, initiating a disease cascade that ultimately manifests as AD (Fig 2G–H). This evidence concerns the gene APOE and Alzheimer disease.