PSEN2 modulates Ca2+ uptake into ER and mitochondria, and its overexpression was observed to increase the interaction between organelles, leading to the increased mitochondrial Ca2+ uptake, activation of the mPTP, activation of calpains, and generation of free radicals underlying learning and memory impairments in fAD-AD models [118,119]. This evidence concerns the gene PSEN2 and Alzheimer disease.