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

Hdl Handle:
http://hdl.handle.net/10147/132290
Title:
Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.
Authors:
Barry, Andrew E; Klyubin, Igor; Mc Donald, Jessica M; Mably, Alexandra J; Farrell, Michael A; Scott, Michael; Walsh, Dominic M; Rowan, Michael J
Affiliation:
Department of Pharmacology and Therapeutics and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland, Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland, and Dublin Brain Bank, Pathology Department, Beaumont Hospital, Dublin 9, Ireland.
Citation:
Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein. 2011, 31 (20):7259-63 J. Neurosci.
Journal:
The Journal of neuroscience : the official journal of the Society for Neuroscience
Issue Date:
18-May-2011
URI:
http://hdl.handle.net/10147/132290
DOI:
10.1523/JNEUROSCI.6500-10.2011
PubMed ID:
21593310
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21593310
Abstract:
Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-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 Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.
Item Type:
Article
Language:
en
ISSN:
1529-2401

Full metadata record

DC FieldValue Language
dc.contributor.authorBarry, Andrew Een
dc.contributor.authorKlyubin, Igoren
dc.contributor.authorMc Donald, Jessica Men
dc.contributor.authorMably, Alexandra Jen
dc.contributor.authorFarrell, Michael Aen
dc.contributor.authorScott, Michaelen
dc.contributor.authorWalsh, Dominic Men
dc.contributor.authorRowan, Michael Jen
dc.date.accessioned2011-05-27T14:50:17Z-
dc.date.available2011-05-27T14:50:17Z-
dc.date.issued2011-05-18-
dc.identifier.citationAlzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein. 2011, 31 (20):7259-63 J. Neurosci.en
dc.identifier.issn1529-2401-
dc.identifier.pmid21593310-
dc.identifier.doi10.1523/JNEUROSCI.6500-10.2011-
dc.identifier.urihttp://hdl.handle.net/10147/132290-
dc.description.abstractSynthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-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 Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21593310en
dc.titleAlzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacology and Therapeutics and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland, Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland, and Dublin Brain Bank, Pathology Department, Beaumont Hospital, Dublin 9, Ireland.en
dc.identifier.journalThe Journal of neuroscience : the official journal of the Society for Neuroscienceen
dc.description.provinceLeinster-
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