PSEN1 and Alzheimer disease: Genetic factors also modulate disease risk: the apolipoprotein E (ApoE) ε4 allele is the strongest known genetic susceptibility factor for late-onset AD [27,28], whereas mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) cause rare familial forms of early-onset AD [29].