PSEN1 and Alzheimer disease: It is hypothesized that the downstream molecule for TRPC6-mediated SOCE in hippocampal neurons is CaMKII since upregulation of neuronal SOCE activity recovers phosphorylation of CaMKII, restores the number of mushroom spines in hippocampal neurons in mouse models of AD [38,39], and induces long-term potentiation in PS1-KI, APP-KI, and 5xFAD hippocampal slices [14,21].