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

Neurobiol Aging. 2020 Jan:85:155.e1-155.e4. doi: 10.1016/j.neurobiolaging.2019.05.018. Epub 2019 May 31.

Abstract

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.

Keywords: Alzheimer's disease; Novel mutation; PSEN1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Asian People / genetics*
  • HEK293 Cells
  • Humans
  • Mutation, Missense*
  • Pedigree*
  • Peptide Fragments / metabolism
  • Presenilin-1 / genetics*

Substances

  • Amyloid beta-Peptides
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)