Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late‐onset Alzheimer's disease

M. L. Peacock, D. L. Murman, A. A.F. Sima, J. T. Warren, A. D. Roses, J. K. Fink

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Amyloid plaques in Alzheimer's disease contain β‐amyloid, encoded by portions of exons 16 and 17 of the amyloid precursor protein. The specific association of rare amyloid precursor protein mutations with some kindreds with early‐onset familial Alzheimer's disease suggests that specific abnormalities in amyloid precursor protein may contribute to the pathogenesis of Alzheimer's disease. Until now, there has been no evidence suggesting that amyloid precursor protein mutations could be involved in late‐onset or sporadic Alzheimer's disease. We used reverse transcription–polymerase chain reaction, denaturing gradient gel electrophoresis, and direct DNA sequencing to analyze amyloid precursor protein exons 16 and 17 from postmortem cerebellar samples from patients with histologically confirmed Alzheimer's disease and control subjects. We found a novel point mutation, substitution of cytosine for guanine, at nucleotide 2119 (amyloid precursor protein 770 messenger RNA transcript) in a patient with late‐onset Alzheimer's disease. This substitution deletes a BglII site and substitutes aspartate for glutamine at codon 665. Denaturing gradient gel electrophoresis analysis showed that this mutation was absent in 40 control subjects and 127 dementia patients. Whether this mutation is a rare but normal variant or contributes to the development of Alzheimer's disease is not known. The BglII restriction fragment length polymorphism enables investigators to determine the frequency of this polymorphism in normal subjects and Alzheimer's disease patients.

Original languageEnglish (US)
Pages (from-to)432-438
Number of pages7
JournalAnnals of Neurology
Issue number4
StatePublished - Apr 1994

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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