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

作者：Barry Andrew E; Klyubin Igor; Mc Donald Jessica M; Mably Alexandra J; Farrell Michael A; Scott Michael; Walsh Dominic M; Rowan Michael J^*

来源：Journal of Neuroscience, 2011, 31(20): 7259-7263.

DOI：10.1523/JNEUROSCI.6500-10.2011

Synthetic amyloid-beta protein (A beta) 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 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 PrP(C), prevented the inhibition of LTP by AD brain-derived A beta. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of A beta, did not significantly affect the A beta-mediatedinhibition of LTP.

• 出版日期2011-5-18