Affiliations: [a] Lennard-Jones Laboratories, The Birchall Centre, Keele University, Staffordshire, UK | [b] Life Sciences, Keele University, Staffordshire, UK | [c] Department of Clinical Neurology, University of Oxford, Oxford, UK | [d] Department of Neuropathology, Oxford Radcliffe NHS Trust, Oxford, UK
Correspondence:
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Correspondence to: Christopher Exley, Lennard-Jones Laboratories, The Birchall Centre, Keele University, Stoke-on-Trent, Staffordshire, ST5 5BG, UK. Tel.: +44 1782 734080; Fax: +44 1782 712378; E-mail: c.exley@chem.keele.ac.uk.
Abstract: The deposition in the brain of amyloid-β as beta sheet conformers associated with senile plaques and vasculature is frequently observed in Alzheimer's disease. While metals, primarily aluminum, iron, zinc, and copper, have been implicated in amyloidβ deposition in vivo, there are few data specifically relating brain metal burden with extent of amyloid pathologies in human brains. Herein brain tissue content of aluminum, iron, and copper are compared with burdens of amyloid-β, as senile plaques and as congophilic amyloid angiopathy, in 60 aged human brains. Significant observations were strong negative correlations between brain copper burden and the degree of severity of both senile plaque and congophilic amyloid angiopathy pathologies with the relationship with the former reaching statistical significance. While we did not have access to the dementia status of the majority of the 60 brain donors, this knowledge for just 4 donors allowed us to speculate that diagnosis of dementia might be predicted by a combination of amyloid pathology and a ratio of the brain burden of copper to the brain burden of aluminum. Taking into account only those donor brains with either senile plaque scores ≥4 and/or congophilic amyloid angiopathy scores ≥12, a Cu : Al ratio of <20 would predict that at least 39 of the 60 donors would have been diagnosed as suffering from dementia. Future research should test the hypothesis that in individuals with moderate to severe amyloid pathology low brain copper is a predisposition to developing dementia.
