APP and Alzheimer disease: In addition, ES aggravated Aβ pathology in 4-month-old bi-genic APP and Tau mutant (biAT) mice and in APPswe/PS1dE9 mice at 9–10 months of age, two models that both overexpress AD related genetic variants and present with AD related neuropathology (Lesuis et al., 2016; Hoeijmakers et al., 2017; Hui et al., 2017).