PSEN2 and Alzheimer disease: FD accounts for 1–5% of all AD cases.11–15 In the early 1990s, linkage analyses of early-onset FD determined that mutations in three genes, namely, amyloid-beta A4 precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), are involved in FD.