Moreover, mutant PS-1 interacts with the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R)-associated Ca2+ release channel, resulting in Ca2+ signalling abnormalities [141, 142] that have been suggested to be an early pathogenic event in AD involved in presynaptic dysfunction [143]. This evidence concerns the gene PSEN1 and Alzheimer disease.