A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid

Nat Genet. 1992 Aug;1(5):345-7. doi: 10.1038/ng0892-345.


Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co-segregates with the disease in two large (probably related) early-onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / genetics*
  • Base Sequence
  • Brain / pathology
  • Codon / genetics
  • Exons
  • Female
  • Genetic Linkage
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Pedigree
  • Point Mutation*
  • Transcription, Genetic


  • Amyloid beta-Protein Precursor
  • Codon
  • Oligodeoxyribonucleotides