Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein

Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2295-300. doi: 10.1073/pnas.0911829107. Epub 2010 Jan 19.


Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-beta (Abeta) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Abeta are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Abeta-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Abeta(1-42) oligomers impaired consolidation of the long-term recognition memory, whereas mature Abeta(1-42) fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Abeta antibody. It has been suggested that the cellular prion protein (PrP(C)) mediates the impairment of synaptic plasticity induced by Abeta. We confirmed that Abeta(1-42) oligomers interact with PrP(C), with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cognition Disorders / etiology
  • Cognition Disorders / metabolism
  • Humans
  • Injections, Intraventricular
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • PrPC Proteins / metabolism*
  • Prion Proteins
  • Prions / genetics
  • Prions / metabolism
  • Protein Binding
  • Surface Plasmon Resonance


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