Synthetic dityrosine-linked β-amyloid dimers form stable, soluble, neurotoxic oligomers
Date
2013
Authors
Kok, W.
Cottam, J.
Ciccotosto, G.
Miles, L.
Karas, J.
Scanlon, D.
Roberts, B.
Parker, M.
Cappai, R.
Barnham, K.
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Journal article
Citation
Chemical Science, 2013; 4(12):4449-4454
Statement of Responsibility
W. Mei Kok, Jade M. Cottam, Giuseppe D. Ciccotosto, Luke A. Miles, John A. Karas, Denis B. Scanlon, Blaine R. Roberts, Michael W. Parker, Roberto Cappai, Kevin J. Barnham and Craig A. Hutton
Conference Name
Abstract
Substantial evidence suggests that soluble oligomers of Aβ are the neurotoxic form resulting in progression of Alzheimer's disease (AD). Tyrosine-10 has been identified as a pivotal residue in the neurotoxicity of Aβ and dityrosine cross-linked Aβ dimers have been proposed as the physiologically relevant Aβ species linked to the progression of AD. We describe the synthesis and characterization of dityrosine-linked Aβ dimers and demonstrate that, in contrast to other covalently linked Aβ dimers, dityrosine-linked Aβ dimers form discrete, stable, soluble aggregates. Furthermore, dityrosine-linked Aβ dimers display increased toxicity in a neuronal cell-line assay compared with the corresponding monomer, consistent with the hypothesis that dityrosine-linked Aβ dimers are implicated in the progression of AD.
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This journal is © The Royal Society of Chemistry 2013