ESR1 and Alzheimer disease: Although unacceptable side-effects preclude the use of estrogen-based therapies for patients at risk of AD (Dumanski et al., 2017; Manson et al., 2013; Shumaker et al., 2004), a variety of SERMs that target specific estrogen receptors (ER) have been shown to confer many of the neuroprotective benefits of E2 (Pandey et al., 2016; Wang et al., 2020; Zhao et al., 2013) suggesting that they might provide an alternative treatment strategy.