Also, there are elevated levels of RYR expression in various mouse models of AD; PSEN1-M146V, PSEN2-N141I, 3XTg-AD and TgCRND8, which lead to an increase in calcium release from IP3- and caffeine-gated stores in hippocampal and cortical neurons [61,62]. This evidence concerns the gene PSEN1 and Alzheimer disease.