ApoE Variants in Sei Whale (Balaenoptera borealis): From the perspective of Cetaceans and ‘Alzheimer’s-like’ Pathology

Alzheimer’s disease study has been limited by the scarcity of natural models replicating ispontaneous disease development. Natural models of “Alzheimer’s-like” pathologies could expand our understanding disease mechanisms and their environmental interactions, offering translational insight and more accurate experimental models. Recent evidence of Aβ plaques and Tau tangles in cetaceans suggests an “Alzheimer’s-like” pathology in this group, whose research interest is expanded by their longevity, prolonged postmenopause, and oxidative damage protection mechanisms; factors underlaying the pathology. ApoE, the main genetic risk factor for sporadic Alzheimer's, remains structurally uncharacterized in cetaceans. Following a 2015 sei whale (Balaenoptera borealis) mass stranding in Chile, two novel ApoE variants (S22R, S112R) were identified in structurally relevant regions via AlphaFold-predicted structures, potentially influencing neurodegeneration analogously to pathogenic human ApoE variants.