A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy

Neurosci Lett. 1997 Aug 22;232(1):29-32. doi: 10.1016/s0304-3940(97)00569-7.


A number of missense mutations associated with early-onset familial Alzheimer's disease have been reported in the presenilin-1 gene. The mutations were demonstrated to cluster in specific regions of the the protein. We report here a novel missense mutation at the C-terminus of the third transmembrane domain in the presenilin-1 protein in a family of Japanese origin with early-onset Alzheimer's disease. This mutation is located at a site that is different from the sites at which mutations are known to cluster. Although the clinical phenotype is similar to those of pedigrees associated with other presenilin-1 mutations, postmortem examination of this pedigree revealed heavy amyloid deposits in the walls of small meningeal arteries as well as around small vessels within the brain parenchyma. These results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis*
  • Cerebral Arteries / pathology*
  • Family Health
  • Female
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Presenilin-1


  • Amyloid beta-Peptides
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1

Associated data

  • GENBANK/L76518
  • GENBANK/L76519
  • GENBANK/L76520
  • GENBANK/L76521
  • GENBANK/L76522
  • GENBANK/L76523
  • GENBANK/L76524
  • GENBANK/L76525
  • GENBANK/L76526
  • GENBANK/L76527
  • GENBANK/L76528