Synthetic Amyloid-beta Oligomers Impair Long-term Memory Independently of Cellular Prion Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Feb 6

PMID 20133875

Citations 239

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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