Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

J Neurol Sci. 2008 May 15;268(1-2):124-30. doi: 10.1016/j.jns.2007.11.021. Epub 2008 Jan 9.

Abstract

Background: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features.

Methods and results: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation).

Conclusions: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations.

Publication types

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

MeSH terms

  • Alanine / genetics
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Protein Precursor / genetics*
  • Blood Pressure
  • DNA Mutational Analysis
  • Electroencephalography
  • Family Health
  • Humans
  • Iran / ethnology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation*
  • Peptide Fragments / cerebrospinal fluid
  • Threonine / genetics

Substances

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