APP and Alzheimer disease: Moreover, there is evidence of enhanced ER-mitochondria crosstalk in cells from FAD patients with mutations in PSEN1, PSEN2, and APP, as well as patients with sporadic AD (Area-Gomez et al., 2012) and enhanced ER to mitochondrial Ca2+ transfer is observed in cells expressing FAD-mutant PSEN2 (Zampese et al., 2011).