Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis

Ann Neurol. 2000 Feb;47(2):249-53. doi: 10.1002/1531-8249(200002)47:2<249::aid-ana18>3.0.co;2-8.

Abstract

A novel missense mutation, Leu723Pro, in the amyloid precursor protein (APP) gene was discovered in an early-onset Alzheimer's disease family. Expression of L723P mutant APP complementary DNA in CHO cells resulted in a 1.4- to 1.9-fold increased production of the 42(43)-amino acid length amyloid beta peptide compared with the wild-type sequence and was capable of causing apoptosis. The mutation is predicted to alter the luminal transmembrane length and helical arrangement of the APP molecule and thus affect the gamma-secretase cleavage site.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Apoptosis / physiology*
  • Base Sequence / genetics
  • CHO Cells / metabolism
  • Cricetinae
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense / physiology*
  • Pedigree
  • Peptide Fragments / metabolism*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (1-43)