Early-onset familial Alzheimer's disease (EOFAD)

Can J Neurol Sci. 2012 Jul;39(4):436-45. doi: 10.1017/s0317167100013949.

Abstract

Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

Publication types

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

MeSH terms

  • Age of Onset
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / genetics
  • Diagnosis, Differential
  • Genetic Counseling
  • Humans
  • Membrane Proteins / genetics*
  • Models, Biological
  • Mutation / genetics*
  • Presenilin-1 / genetics
  • Presenilin-2

Substances

  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • Presenilin-1
  • Presenilin-2