PSEN2 and Alzheimer disease: The authors also showed that two familial mutants of PS2 (T122R and N141I), known to be involved in Ca2+ release during atypical dementia and Aβ42 production during AD, are more efficient in ER-mitochondria tethering than wild type (WT) PS2, increasing mitochondrial Ca2+ uptake upon ER Ca2+ release [46,173].