MAPT and Alzheimer disease: These data are intriguing considering the strong protective effect of E2 with a later age at AD onset and lower levels of Aβ plaques and tau tangles in those carrying two copies of APOE ε2 or one copy of APOE ε2 and one copy of APOE ε3 (Reiman et al., 2020) and the beneficial effects of the APOE3 Christchurch (R136S) mutation reported in an individual who carried a PS1 mutation (Arboleda-Velasquez et al., 2019).