APOE and Alzheimer disease: Of these, rs877973 and rs565782572 have not been linked to neurodegeneration or cardiovascular disease, while rs440446, rs769449, and rs769450 are chiefly involved in AD, and the combination of alleles carried by variants rs429358 and rs7412 concur to define the three main isoforms of the APOE protein: ε2 (mostly protective against neurodegeneration, but involved in cerebral amyloid angiopathy, CAA), ε3 (the “wild-type”, or most common isoform worldwide), and ε4 (most probably the ancestral isoform, chiefly linked to Alzheimer’s and cardiovascular disease).