Data interpretation concerning some controversial results about RyR deregulation in AD must take in consideration the divergence of study systems i.e.: i) simple versus double or triple transgenic mice models; ii) primary cultures neurons and acute hippocampal slices versus neuronal derived cell lines or fibroblasts; and most importantly iii) the time course of “AD pathogenesis” development in each study model. The gene discussed is RYR1; the disease is Alzheimer disease.