PSEN2 and Alzheimer disease: Importantly, elevated ER to mitochondrial contact and crosstalk has been observed in PSEN1 and PSEN2 knockout cells, in cells expressing FAD mutant PSEN2, and in skin fibroblasts from FAD and sporadic AD patients (Area-Gomez et al., 2012; Filadi et al., 2016; Kipanyula et al., 2012; Zampese et al., 2011).