The significance of the APOE gene in governing AD risk was initially recognized in the 1990s, with a series of pioneering studies providing the crucial genotype-to-pathology association and evidence of the physical protein-to-biomarker interaction (Corder et al, 1993; Saunders et al, 1993; Strittmatter et al, 1993). This evidence concerns the gene APOE and Alzheimer disease.