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      Aluminium, iron and copper in human brain tissues donated to the medical research council's cognitive function and ageing study

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          Abstract

          Aluminium, iron and copper are all implicated in the aetiology of neurodegenerative diseases including Alzheimer's disease. However, there are very few large cohort studies of the content of these metals in aged human brains. We have used microwave digestion and TH GFAAS to measure aluminium, iron and copper in the temporal, frontal, occipital and parietal lobes of 60 brains donated to the Cognitive Function and Ageing Study. Every precaution was taken to reduce contamination of samples and acid digests to a minimum. Actual contamination was estimated by preparing a large number of (170+) method blanks which were interspersed within the full set of 700+ tissue digests. Subtraction of method blank values (MBV) from tissue digest values resulted in metal contents in all tissues in the range, MBV to 33 μg g(-1) dry wt. for aluminium, 112 to 8305 μg g(-1) dry wt. for iron and MBV to 384 μg g(-1) dry wt. for copper. While the median aluminium content for all tissues was 1.02 μg g(-1) dry wt. it was informative that 41 brains out of 60 included at least one tissue with an aluminium content which could be considered as potentially pathological (> 3.50 μg g(-1) dry wt.). The median content for iron was 286.16 μg g(-1) dry wt. and overall tissue iron contents were generally high which possibly reflected increased brain iron in ageing and in neurodegenerative disease. The median content for copper was 17.41 μg g(-1) dry wt. and overall tissue copper contents were lower than expected for aged brains but they were commensurate with aged brains showing signs of neurodegenerative disease. In this study we have shown, in particular, the value of carrying out significant numbers of method blanks to identify unknown sources of contamination. When these values are subtracted from tissue digest values the absolute metal contents could be considered as conservative and yet they may still reflect aspects of ageing and neurodegenerative disease in individual brains. This journal is © The Royal Society of Chemistry 2012

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          Iron, zinc and copper in the Alzheimer's disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion.

          Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer's disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p<0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Medicinal inorganic chemistry approaches to passivation and removal of aberrant metal ions in disease.

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              Detection and quantification limits: origins and historical overview1Adapted from the Proceedings of the 1996 Joint Statistical Meetings (American Statistical Association, 1997). Original title: “Foundations and future of detection and quantification limits”. Contribution of the National Institute of Standards and Technology; not subject to copyright.1

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                Author and article information

                Journal
                METAIR
                Metallomics
                Metallomics
                Royal Society of Chemistry (RSC)
                1756-5901
                1756-591X
                2012
                2012
                : 4
                : 1
                : 56-65
                Article
                10.1039/C1MT00139F
                22045115
                fbd9aa64-29d8-4a2e-82ed-e6c97c3f6c67
                © 2012
                History

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