In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 5 ( 2010-02-02), p. 2295-2300
Abstract:
Inability to form new memories is an early 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 Aβ 1–42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ 1–42 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 (PrP C ) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ 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 Aβ 1–42 oligomers are responsible for cognitive impairment in AD and that PrP C is not required.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0911829107
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2010
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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