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Issue 12, 2013
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Synthetic dityrosine-linked β-amyloid dimers form stable, soluble, neurotoxic oligomers

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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.

Graphical abstract: Synthetic dityrosine-linked β-amyloid dimers form stable, soluble, neurotoxic oligomers

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Publication details

The article was received on 21 Dec 2012, accepted on 04 Sep 2013 and first published on 09 Sep 2013


Article type: Edge Article
DOI: 10.1039/C3SC22295K
Chem. Sci., 2013,4, 4449-4454

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    Synthetic dityrosine-linked β-amyloid dimers form stable, soluble, neurotoxic oligomers

    W. M. Kok, J. M. Cottam, G. D. Ciccotosto, L. A. Miles, J. A. Karas, D. B. Scanlon, B. R. Roberts, M. W. Parker, R. Cappai, K. J. Barnham and C. A. Hutton, Chem. Sci., 2013, 4, 4449
    DOI: 10.1039/C3SC22295K

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