期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：5
页码：2295-2300
DOI：10.1073/pnas.0911829107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-{beta} (A{beta}) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of A{beta} are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of A{beta}-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic A{beta}1-42 oligomers impaired consolidation of the long-term recognition memory, whereas mature A{beta}1-42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-A{beta} antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by A{beta}. We confirmed that A{beta}1-42 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 A{beta}1-42 oligomers are responsible for cognitive impairment in AD and that PrPC is not required.
关键词：Alzheimer ; neurotoxicity ; object recognition test ; surface plasmon resonance ; protein aggregation
