APP and Alzheimer disease: In AD models, such as PS1-KI and APP-KI, dendritic spines of hippocampal neurons are lost both in vitro and in vivo, indicating that the loss of mushroom-shaped “memory spines” reflects cognitive decline, learning, and memory deficits in AD (Ryskamp et al., 2019; Fisher et al., 2015), suggesting the involvement of reduced S1R in AD pathology.