Systematic genetic study of Alzheimer disease in Latin America: Mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia

Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer d isease (EOAD, onset age at or before 65 years). In order to assess the gene tic contribution of these genes in a series of Colombian AD cases, we perfo rmed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset less than or equal to 65 years). No APP missense mutations were identified. In three autosomal domi nant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset a utosomal AD cases: an I143T mutation in one case (onset age 30 years) and a n E280A mutation in two other cases (onset ages 35 and 42 years). In additi on, a novel PSEN1 V94M mutation was present in one early-onset AD case with out known family history (onset age 53 years) and absent in 53 controls. Th e E318G polymorphism was present in five AD cases and absent in controls. I n PSEN2, two different silent mutations were detected, including one not re ported elsewhere (P129). The majority of the Colombian AD cases, predominan tly late-onset, were negative for PSEN and APP mutations. (C) 2001 Wiley-Li ss, Inc.