[Alzheimer disease: autosomal dominant forms]

Rev Neurol (Paris). 2009 Mar;165(3):223-31. doi: 10.1016/j.neurol.2008.10.019. Epub 2008 Dec 10.
[Article in French]

Abstract

We propose a review devoted to the autosomal dominant forms of Alzheimer disease (AD). These forms are the consequences of either PSEN1 mutations (69%), APP mutations (1%), or APP duplication (7.5%), and exceptionally of PSEN2 mutations (2%). The main characteristic of these AD forms is the early age of onset usually before the age of 60 years. The first part of the review focuses on the identification of unusual clinical and neuropathological phenotypes enlarging the AD spectrum: intracerebral hemorrhages caused by severe amyloid angiopathy, spastic paraparesis, Lewy body dementia and exceptional cerebellar ataxia. The second part concerns the consequences of these mutations on A beta processing, thus demonstrating the key role of the causal "amyloid cascade".

Publication types

  • English Abstract

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / physiopathology
  • Genes, Dominant / genetics*
  • Humans
  • Middle Aged
  • Mutation / physiology
  • Phenotype
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics

Substances

  • Amyloid beta-Protein Precursor
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2