PSEN1 and Alzheimer disease: Moreover, we found that some, but not all, FAD PS mutations disrupt Ca2+ leak function (Tu et al., 2006; Nelson et al., 2007, 2010), leading to the overfilling of ER with Ca2+ and exaggerated ER Ca2+ release observed in PS1/PS2 FAD mutants fibroblasts (Tu et al., 2006; Nelson et al., 2007, 2010), cultured hippocampal neurons from 3xTg AD neurons (Zhang et al., 2010b), and primary lymphoblasts from FAD patients (Nelson et al., 2010).