A Novel PSEN1 Mutation (I238M) associated with Early-Onset Alzheimer's Disease in an African-American Woman

作者：Ting Simon Kang Seng; Benzinger Tammie; Kepe Vladimir; Fagan Anne; Coppola Giovanni; Porter Verna; Hecimovic Silva; Chakraverty Suma; Alvarez Retuerto Ana Isabel; Goate Alison; Ringman John M^*

来源：Journal of Alzheimer's Disease, 2014, 40(2): 271-275.

DOI：10.3233/JAD-131844

• African
• Alzheimer's disease
• amyloid-beta(42)
• autosomal dominant
• familial
• gamma-secretase
• in vitro
• PIB-PET
• presenilin-1
• PSEN1

Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of A beta(42) in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.

• 出版日期2014