Intracellular A-beta amyloid, a sign for worse things to come?

Mol Neurobiol. Oct-Dec 2002;26(2-3):299-316. doi: 10.1385/MN:26:2-3:299.

Abstract

In this review the authors discuss the possible neuropathological role of intracellular amyloid-beta accumulation in Alzheimer's disease (AD) pathology. There is abundant evidence that at early stages of the disease, prior to A-beta amyloid plaque formation, A-beta peptides accumulate intraneuronally in the cerebral cortex and the hippocampus. The experimental evidence would indicate that intracellular amyloid-beta could originate both by intracellular biosynthesis and also from the uptake of amyloidogenic peptides from the extracellular milieu. Herein the aspects of the possible impact of intracellular amyloid-beta in human AD pathology are discussed, as well as recent observations from a rat transgenic model with a phenotype of intracellular accumulation of A-beta fragments in neurons of the hippocampus and cortex, without plaque formation. In this model, the intracellular amyloid-beta phenotype is accompanied by increased MAPK/ERK activity and tau hyperphosphorylation. Finally, the authors discuss the hypothesis that, prior to plaque formation, intracellular A-beta accumulation induces biochemical and pathological changes in the brain at the cellular level priming neurons to further cytotoxic attack of extracellular amyloidogenic peptides.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Intracellular Fluid / metabolism*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins