PSEN1 and familial Alzheimer disease: Approximately 5% of AD cases are caused by missense mutations of three genes: presenilin 1 (PSEN1), PSEN2, and amyloid precursor protein (APP), leading to the accumulation of Aβ and disease onset before the age of 65 [3,4]; this type of AD is known as early-onset familial AD (fAD).