Journal article

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

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, Craig A Hutton



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..

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Awarded by Australian Research Council

Funding Acknowledgements

This research was supported by grants from the Australian Research Council (DP120101254) and the National Health and Medical Research Council of Australia (NHMRC). We acknowledge infrastructure support from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute. K.J.B. and M.W.P. are NHMRC Fellows.