RYR2 and Alzheimer disease: However, the fact that stabilization of RyR2 through increased binding affinity to CaM almost completely inhibited TAU phosphorylation in either TM-induced AD-type cells or neural cells from AppNL-G-F mice strongly suggests that destabilization of RyR2 is an upstream of TAU phosphorylation in the pathogenesis of AD (Supplementary Fig. 8).