APP and familial Alzheimer disease: Familial AD (fAD) is a rare form of AD that is primarily caused by genetic mutations in three genes: the amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene, and presenilin 2 (PSEN2) gene.5–10 Mutations of PSEN1 and PSEN2 genes affect the function of γ-secretase complex, which is responsible for the cleavage of the APP protein and releasing Aβ peptides, leading to increased ratio of Aβ42/Aβ40, which contributes to the formation of amyloid plaques.