The present findings, which are in accord with our previous in vitro results (Paula-Lima et al., 2011; Lobos et al., 2016; SanMartin et al., 2017) definitively constitute a substantial evidence that AβOs cause the RyR2 decrease reported in AD patients at early stages of the disease (Kelliher et al., 1999). This evidence concerns the gene RYR2 and Alzheimer disease.