PSEN1 and Alzheimer disease: Altered Ca2+ homeostasis is a very early sign of cell dysfunction in AD patients [129,130,131,132] and mutant presenilins (PSEN1 and PSEN2), associated with the majority of familial AD (FAD) cases, have been implicated in AD-related Ca2+ dysregulation, through different mechanisms, often independent from their γ-secretase activity [133].