Our initial study examined female EFAD (APOE-TR/5xFAD-Tg+/-) mice carrying transgenes for familial AD genes (5xFAD) together with human APOE alleles by targeted replacement (APOE-TR), which had APOE-e3+/+ (E3; APOE3) or APOE-e4+/+ (E4; APOE4) genotype. Here, APOE is linked to Alzheimer disease.