PSEN1 and Alzheimer disease: Despite a number of rare mutations on the Aβ precursor protein (APP), Presenilin-1 (PS1) and Presenilin-2 (PS2) relating to familial AD, which account for less than 2% of all AD cases, the apolipoprotein E (APOE) ε4 allele remains the strongest genetic risk factor for sporadic AD.