PSEN1 and Alzheimer disease: Although the genetic cause of familial AD (FAD) has been identified and well characterized through highly penetrant variants in APP (Goate et al., 1991), PSEN1 (Sherrington et al., 1995), and PSEN2, (Levy-Lahad et al., 1995), these autosomal dominant forms account only for less than 1% of AD cases (Bekris et al., 2010).