APOE and Alzheimer disease: APOE4 genotype increases risk of developing AD over the other alleles APOE2 and APOE3 by 5–10 years (Noguchi et al., 1993; Ossenkoppele et al., 2015; Fisher et al., 2018), and was reported to increase Aβ deposition and oligomer formation, as well as phosphorylated tau within neurons (Riedel et al., 2016; Fisher et al., 2018).