PSEN1 and Alzheimer disease: Eric Schon’s group first demonstrated the enrichment of presenilins in the MAM and suggested that MAM is the predominant subcellular location for PS1/PS2 and gamma secretase activity and later further demonstrated significantly increased MAM function and ER-mitochondrial communication in presenilin-deficient cells and in fibroblasts from patients with both the familial and sporadic forms of AD, suggesting that upregulated MAM function and increased ER-mitochondria crosstalk may be involved in the pathogenesis of AD [60, 62, 63].