APP and Alzheimer disease: Family studies of early-onset AD in the 1990s (Schellenberg et al., 1992) identified causal mutations in amyloid precursor protein (APP;Levy et al., 1990; Van Broeckhoven et al., 1990), presenilin 1 (PSEN1; Campion et al., 1995), and presenilin 2 (PSEN2; Rogaev et al., 1995).