Amyloid-b nanotubes are associated with prion protein-dependent synaptotoxicity

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Title: Amyloid-b nanotubes are associated with prion protein-dependent synaptotoxicity
Authors: Nicoll, Andrew J.
Panico, Silvia
Freir, Darragh
Herron, Caroline
O'Malley, Tiernan
et al.
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Date: 11-Sep-2013
Abstract: Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ(1-42). However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ(1-42) after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer's disease.
Type of material: Journal Article
Publisher: Nature Publishing Group
Copyright (published version): 2013 Macmillan Publishers Limited
Keywords: Alzheimer's diseaseAβ nanotubes
DOI: 10.1038/ncomms3416
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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