PSEN1 and Alzheimer disease: Summarizing several works performed in different AD-related models, two opposite mitochondrial phenotypes (Figure 1B) have been reported so far: (1) a mitochondrial Ca2+ overload, mainly in cells treated with Aβ oligomers and in FAD-PS1-based mouse models; (2) a blunted mitochondrial Ca2+ uptake, mainly in FAD-PS2-based mouse models (Figure 1B).