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

Claudia Balducci, Marten Beeg, Matteo Stravalaci, Antonio Bastone, Alessandra Sclip, Emiliano Biasini, Laura Tapella, Laura Colombo, Claudia Manzoni, Tiziana Borsello, Roberto Chiesa, Marco Gobbi, Mario Salmona, Gianluigi Forloni

Research output: Contribution to journalArticlepeer-review

Abstract

Inability to formnewmemories is anearly clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ1-42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ1-42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ1-42 oligomers interact with PrPC, with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ1-42 oligomers are responsible for cognitive impairment in AD and that PrP C is not required.

Original languageEnglish
Pages (from-to)2295-2300
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number5
DOIs
Publication statusPublished - Feb 2 2010

Keywords

  • Alzheimer
  • Neurotoxicity
  • Object recognition test
  • Protein aggregation
  • Surface plasmon resonance

ASJC Scopus subject areas

  • General

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