APP and Alzheimer disease: The discovery of mutations in three genes (APP, PSEN1 and PSEN2) that cause rare, early-onset and monogenic forms of AD led to the development of the amyloid cascade hypothesis, which postulates that abnormal aggregation and deposition of amyloid β peptide (Aβ is one of the products of APP cleavage by β- and ɣ-secretase, of which PSEN1/2 are two subunits) is neurotoxic and the primary cause of neurodegeneration [4].