Initial studies in fibroblasts from AD patients (Gibson et al., 1996) or in cells bearing the human presenilin 1 (PS1) AD mutation (Begley et al., 1999; Guo et al., 1999; Leissring et al., 1999; LaFerla, 2002; Stutzmann, 2005) found evidence of abnormal Ca2+ release through IP3R pathways (Leissring et al., 1999). Here, PSEN1 is linked to Alzheimer disease.