RT Journal Article SR Electronic T1 Alzheimer's Disease Brain-Derived Amyloid-β-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7259 OP 7263 DO 10.1523/JNEUROSCI.6500-10.2011 VO 31 IS 20 A1 Andrew E. Barry A1 Igor Klyubin A1 Jessica M. Mc Donald A1 Alexandra J. Mably A1 Michael A. Farrell A1 Michael Scott A1 Dominic M. Walsh A1 Michael J. Rowan YR 2011 UL http://www.jneurosci.org/content/31/20/7259.abstract AB Synthetic amyloid-β protein (Aβ) 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 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 PrPC, prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrPC, 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 PrPC in mediating synaptic plasticity disruption by soluble Aβ.