Issue 12, 2013

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
21 dec 2012
Accepted
04 sep 2013
First published
09 sep 2013

Chem. Sci., 2013,4, 4449-4454

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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