For example, APOE4 is associated with learning and memory dysfunction during aging, independent of AD (reviewed in Tai et al., 2016), which is recapitulated in APOE targeted replacement mice (Grootendorst et al., 2005; Villasana et al., 2006; Bour et al., 2008; Rodriguez et al., 2013; Tai et al., 2016; Thomas et al., 2017; Zaldua et al., 2020). This evidence concerns the gene APOE and Alzheimer disease.