Alzheimer's Disease Brain-Derived Amyloid-β-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein

被引：201

作者：

Barry, Andrew E. ^{[1
,2
]}

Klyubin, Igor ^{[1
,2
]}

Mc Donald, Jessica M. ^{[3
]}

Mably, Alexandra J. ^{[3
]}

Farrell, Michael A. ^{[4
]}

Scott, Michael ^{[3
]}

Walsh, Dominic M. ^{[3
]}

Rowan, Michael J. ^{[1
,2
]}

机构：

[1] Trinity Coll Dublin, Dept Pharmacol & Therapeut, Dublin 2, Ireland

[2] Trinity Coll Dublin, Inst Neurosci, Dublin 2, Ireland

[3] Univ Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Dublin 4, Ireland

[4] Beaumont Hosp, Dept Pathol, Dublin 9, Ireland

来源：

JOURNAL OF NEUROSCIENCE | 2011年 / 31卷 / 20期

基金：

爱尔兰科学基金会;

关键词：

SYNAPTIC PLASTICITY; RECEPTOR; OLIGOMERS; MEMORY; IMPAIRMENT; BINDING; HIPPOCAMPUS; DIMERS; STATE;

D O I：

10.1523/JNEUROSCI.6500-10.2011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Synthetic amyloid-beta protein (A beta) oligomers bind with high affinity to cellular prion protein (PrPC), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble A beta in vitro is controversial. Here we report that intracerebroventricular injection of A beta-containing aqueous extracts of Alzheimer's disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of A beta. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative A beta-binding site on PrPC, prevented the inhibition of LTP by AD brain-derived A beta. In contrast, R1, a Fab directed to the C terminus of PrPC, a region not implicated in binding of A beta, did not significantly affect the A beta-mediatedinhibition of LTP. These data support the pathophysiological significance of SDS-stable A beta dimer and the role of PrPC in mediating synaptic plasticity disruption by soluble A beta.

引用

页码：7259 / 7263

页数：5

共 35 条

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