Previous experiments, showing that RyR inhibition reduces the sustained [Ca2+] increase and the subsequent consequent deleterious effects in different experimental AD models, support the hypothesis that RyR channels mediate CICR in AD (Stutzmann et al., 2006; Paula-Lima et al., 2011; Sanmartin et al., 2012; SanMartin et al., 2017). Here, RYR2 is linked to Alzheimer disease.