PSEN1 and Alzheimer disease: It is also interesting to note that, although AD familial cases (which are less than 1% of AD total cases [53]) are principally caused by mutations in genes coding for the amyloid precursor protein (APP) and for the catalytic components of γ-secretase presenilin 1 and 2 (PSEN1 and PSEN2), i.e., the cellular proteases which process APP in Aβ peptide [54], genome-wide association studies (GWASs) have identified several risk loci in genes related to mitochondria functionality.