Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease.

Presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) genes account for the majority of autosomal dominant Alzheimer's disease (AD), with PSEN1 being the most common. We screened these genes for mutations in a Chinese proband from an autosomal dominant early-onset AD pedigree. Early-onset AD is defined as the age at onset of AD < 65 years. A heterozygous variant (c.332G > T) of PSEN1, which results in a missense mutation (p.Gly111Val), was identified. Three prediction programs suggested this mutation was disease causing. When PSEN1 Gly111Val was overexpressed in HEK293/APPswe cells, the ratio of Aβ42/Aβ40 was significantly increased compared with that of wild-type PSEN1. Our results suggest that this novel PSEN1 Gly111Val mutation may play a pathogenic role in AD.