APP and Alzheimer disease: The genetic background has a major role in AD, and DNA variants may contribute, ranging from predisposing risk factors (having from medium to large effect size, such as the ε4 allele of the APOE gene) [2] to full penetrant causal mutations in a few genes, namely presenilins (PSEN1 and PSEN2) and the amyloid-β (A4) precursor protein (APP) [3, 4].