ESR1 and Alzheimer disease: It should be noted that the PI3K/Akt pathway has been linked to the neuroprotective effects of a variety of candidate therapeutic compounds in AD models (Long et al., 2021; Desale et al., 2021; Pan et al., 2024), including SERMs that engage the non-canonical estrogen receptor GPER1 (Deng et al., 2017; Roque and Baltazar, 2019; Upadhayay et al., 2023).