Single-molecule imaging reveals that small amyloid-β1–42 oligomers interact with the cellular prion protein (PrPC)

Kristina A. Ganzinger, Priyanka Narayan, Seema S. Qamar, Laura Weimann, Rohan T. Ranasinghe, Adriano Aguzzi, Christopher M. Dobson, James McColl, Peter St George-Hyslop, David Klenerman

Research output: Contribution to journalArticlepeer-review

35 Citations (SciVal)

Abstract

Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer’s disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ42 have obscured the nature of the oligomeric species that bind to a given receptor. Here, we have used single-molecule imaging to characterize Aβ42 oligomers (oAβ42) and to confirm the controversial interaction of oAβ42 with the cellular prion protein (PrPC) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrPC and that the species bound to PrPC are predominantly small oligomers (dimers and trimers). Single-molecule biophysical studies can thus aid in deciphering the mechanisms that underlie receptor-mediated oAβ-induced neurotoxicity, and ultimately facilitate the discovery of novel inhibitors of these pathways.
Original languageEnglish
Pages (from-to)2515-2521
Number of pages7
JournalChemBioChem
Volume15
Issue number17
DOIs
Publication statusPublished - 24 Nov 2014

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