The role of A beta 42 in Alzheimer's disease

J Physiol Paris. Jun-Aug 1998;92(3-4):289-92. doi: 10.1016/s0928-4257(98)80035-1.

Abstract

Our recent studies of plasma, fibroblasts, transfected cells and transgenic mice show that a fundamental effect of the mutations linked to familial Alzheimer's disease (FAD) is to increase the extracellular concentration of A beta 42. This effect of the FAD-linked mutations is likely to be directly related to the pathogenesis of Alzheimer's disease (AD) because A beta 42 is deposited early and selectively in the senile plaques that are an invariant feature of all forms of AD. Thus our results provide strong evidence that the FAD-linked mutations all cause AD by increasing the extracellular concentration of A beta 42 (43), thereby fostering A beta deposition, and they support the hypothesis that cerebral A beta deposition is an essential early event in the pathogenesis of all forms of AD. Interactions between the basal forebrain cholinergic system and A beta that could influence AD pathogenesis are discussed.

Publication types

  • Review

MeSH terms

  • Age of Onset
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / physiology*
  • Animals
  • Clinical Trials as Topic
  • Humans
  • Mutation
  • Peptide Fragments / physiology*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)