This model recapitulates human clinical presentation of APOE-associated AD, such that female mice expressing two copies of APOE4 (E4FAD) exhibit earlier onset of, and more advanced, disease pathology relative to E4FAD males and mice of both sexes that express two copies of APOE3 (E3FAD) (Youmans et al., 2012; Tai et al., 2014; Liu et al., 2015; Cacciottolo et al., 2016; Balu et al., 2023). Here, APOE is linked to Alzheimer disease.