Two articles in a forthcoming issue of the Journal of Alzheimer’s Disease (Volume 18: 4) by Dr Chris Exley, Reader in Bioinorganic Chemistry in the Research Institute for the Environment, Physical Sciences and Applied Mathematics at Keele University, UK, (“Copper abolishes the beta-sheet secondary structure of preformed amyloid fibrils of Abeta42”) and Dr Zhao-Feng Jiang, of Beijing Union University, Beijing, China (“Coordinating to three histidine residues: Cu(II) promoting oligomeric, fibril amyloid beta peptide to aggregate in a non-beta-sheeted way”) 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 Ab42 in b-sheets in neuritic or senile plaques. The Keele team have shown in previous research in JAD (House et al., (2004) JAD 6, 291-301) that copper (Cu(II)) prevents the deposition of Ab42 in b-sheets while in the current research they show that Cu(II) abolishes the b-sheet structure of preformed amyloid fibrils of Ab42. A similar finding was made by the group of Jiang for the other form of beta amyloid, Ab40, 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 b-sheets of Ab42, 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 b-lactoglobulin. Copper appeared to have a role in the formation of spherulites of Ab42 and this will be investigated in future research. The role of metals in the formation, deposition and metabolism of Ab in Alzheimer’s disease is much debated and these new findings highlight a potential protective role for copper in Alzheimer’s disease.
Dr Chris Exley
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