A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease

Science. 1991 Oct 4;254(5028):97-9. doi: 10.1126/science.1925564.


Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of leptomeningeal vessels. Although most cases of Alzheimer's disease are sporadic, kindreds with autosomal-dominant inheritance of the syndrome suggest that a single mutation may be important in pathogenesis. Direct sequencing of DNA from a family with autopsy-proven Alzheimer's disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and may be the inherited factor causing both amyloid fibril formation and dementia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / genetics*
  • Base Sequence
  • DNA Mutational Analysis
  • Exons
  • Humans
  • Molecular Sequence Data
  • Neurofibrillary Tangles / pathology
  • Pedigree
  • Polymerase Chain Reaction


  • Amyloid beta-Protein Precursor

Associated data

  • GENBANK/M64709
  • GENBANK/M76239
  • GENBANK/M76240
  • GENBANK/M76241
  • GENBANK/M76242
  • GENBANK/M76243
  • GENBANK/M76244
  • GENBANK/M83742
  • GENBANK/S57665
  • GENBANK/S70464