Two articles in a forthcoming issue of the Journal of Alzheimer’s Disease -- by Dr Chris Exley, Reader in Bioinorganic Chemistry in the Research Institute for the Environment, Physical Sciences and Applied Mathematics at Keele University, UK, and Dr Zhao-Feng Jiang, of Beijing Union University, Beijing, China -- have confirmed a potentially protective role for copper in Alzheimer’s disease.
Previous research has shown that copper is one component of the amyloid beta plaques which are found in the brains of people of Alzheimer’s disease.
A central tenet of the Amyloid Cascade Hypothesis of Alzheimer’s disease is the aberrant deposition in the brain of Aβ42 in β-sheets in neuritic or senile plaques. The Keele team have shown in previous research in JAD that copper (Cu(II)) prevents the deposition of Aβ42 in β-sheets while in the current research they show that Cu(II) abolishes the β-sheet structure of preformed amyloid fibrils of Aβ42. A similar finding was made by the group of Jiang for the other form of beta amyloid, Aβ40, and together these observations strongly suggest that copper prevents both the formation and the accumulation of plaques in the brain.
Coincident with the copper-catalysed dissolution of β-sheets of Aβ42, Exley’s group made the first observation of the in vitro formation of spherulites of this peptide. These spherical globules of amyloid have only previously been observed in vitro for the other amyloid-forming proteins insulin and β-lactoglobulin. Copper appeared to have a role in the formation of spherulites of Aβ42 and this will be investigated in future research. The role of metals in the formation, deposition and metabolism of Aβ in Alzheimer’s disease is much debated and these new findings highlight a potential protective role for copper in Alzheimer’s disease.
- Emily House, Matthew Mold, Joanna Collingwood, Alex Baldwin, Steven Goodwin and Christopher Exley. Copper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-β. Journal of Alzheimer's Disease, 2009; DOI: 10.3233/JAD-2009-1235
- Xiao-Hui Yang, Han-Chang Huang, Lin Chen, Wei Xu and Zhao-Feng Jiang. Coordinating to Three Histidine Residues: Cu(II) Promotes Oligomeric and Fibrillar Amyloid-β Peptide to Precipitate in a Non-β Aggregation Way. Journal of Alzheimer's Disease, 2009; DOI: 10.3233/JAD-2009-1186
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