This is, on the one hand, consistent with previous in vitro studies demonstrating that raising E2 levels by adding directly to the culture medium leads to a decrease in Aβ(1–42) (Xu et al., 1998, 2006; Liang et al., 2010), on the other hand, this indicates a protective role of local E2 in the acute/early stages of AD, since our previous studies found stable or slightly increased EGR1 and AChE expression in the NBM and the PFC, which may contribute to maintaining cognitive function in early AD (Bossers et al., 2010; Zhu et al., 2016; Hu et al., 2019). The gene discussed is EGR1; the disease is Alzheimer disease.