APP and Alzheimer disease: The most accepted hypothesis is the amyloid cascade hypothesis because it is supported by the genetics of early-onset familial AD (mutations in amyloid precursor protein (APP), presenilin 1 (PS1; also known as PSEN1) and PS2 (also known as PSEN2) genes), and late-onset AD (ε4 allele of the apolipoprotein E (APOE) gene) [28].