Beta-amyloid oligomers and cellular prion protein in Alzheimer's disease

J Mol Med (Berl). 2010 Apr;88(4):331-8. doi: 10.1007/s00109-009-0568-7. Epub 2009 Dec 4.

Abstract

Prefibrillar oligomers of the beta-amyloid peptide (A beta) are recognized as potential mediators of Alzheimer's disease (AD) pathophysiology. Deficits in synaptic function, neurotoxicity, and the progression of AD have all been linked to the oligomeric A beta assemblies rather than to A beta monomers or to amyloid plaques. However, the molecular sites of A beta oligomer action have remained largely unknown. Recently, the cellular prion protein (PrP(C)) has been shown to act as a functional receptor for A beta oligomers in brain slices. Because PrP(C) serves as the substrate for Creutzfeldt-Jakob Disease (CJD), these data suggest mechanistic similarities between the two neurodegenerative diseases. Here, we review the importance of A beta oligomers in AD, commonalities between AD and CJD, and the newly emergent role of PrP(C) as a receptor for A beta oligomers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / blood*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics*
  • Animals
  • Brain / pathology
  • COS Cells
  • Chlorocebus aethiops
  • Creutzfeldt-Jakob Syndrome / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases / pathology
  • Peptide Fragments / chemistry
  • PrPC Proteins / chemistry
  • Prions / chemistry
  • Prions / metabolism*

Substances

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