In light of the amyloid burden and synaptic degeneration previously observed in 6 month-old female E3FAD and E3/4FAD mice (Youmans et al., 2012; Tai et al., 2014; Liu et al., 2015; Cacciottolo et al., 2016; Balu et al., 2023), these findings suggest the exciting possibility that ERβ agonist treatment may not only be beneficial for recognition memory in menopausal women without dementia, but also in APOE3/3+ and APOE3/4+ women with symptoms of cognitive decline. This evidence concerns the gene ESR2 and Mental deterioration.