Journal
METALLOMICS
Volume 12, Issue 6, Pages 952-962Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0mt00048e
Keywords
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Categories
Funding
- Endocore Research Associates, New Zealand [60147]
- Maurice and Phyllis Paykel Trust, New Zealand [3627036]
- Lottery Health New Zealand [3626585, 3702766]
- Maurice Wilkins Centre for Molecular Biodiscovery, New Zealand [9341-3622506]
- Lee Trust, New Zealand
- University of Auckland [JXU058]
- Oakley Mental Health Research Foundation [3456030, 3627092, 3701339, 3703253, 3702870]
- Ministry of Business, Innovation & Employment, New Zealand [UOAX0815]
- Neurological Foundation of New Zealand
- Medical Research Council [UK] [MR/L010445/1, MR/L011093/1]
- Alzheimer's research UK [ARUK-PPG2014B-7]
- University of Manchester
- CMFT
- Northwest Regional Development Agency
- MRC [MR/N028457/1, MR/L011093/1, MR/L010445/1, MR/L023784/1, MR/L023784/2] Funding Source: UKRI
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Studies of neurodegenerative conditions such as Alzheimer's disease (AD) usingpost mortembrain tissues have uncovered several perturbations in metals such as copper, iron, and zinc. However, studies of the effects of key, potentially confounding variables on these tissues are currently lacking. Moreover, human-brain tissues have limited availability, further enhancing the difficulty of matching potentially-significant variables including age, sex-matching, post-mortem delay (PMD), and neuropathological stage. This study aimed to investigate the effects of such factors and how they might influence metal concentrations in post-mortem brains. Cingulate gyrus from AD cases and matched controls was obtained from two brain banks, based in Auckland, New Zealand and Manchester, UK. Inductively-coupled plasma mass spectrometry (ICP-MS) was employed to measure levels of nine essential metals in brain tissues, and compared concentrations between cases and controls, and between cohorts, to analyse effects of age, sex, Braak stage, brain weight, and PMD. The same methods were used to investigate the effects of PMD under more controlled conditions usingex vivohealthy adult rat-brain tissue. Metal concentrations in human brain were found to be unmodified by differences in age, sex-matching, Braak stage, brain weight, and PMD between cohorts. Some metals were, however, found to vary significantly across different regions in rat brains. These results indicate that investigations of metal homeostasis in AD and other neurodegenerative conditions can be reliably performed using brain tissues without confounding by varying PMD, age, sex-matching, brain weight, and Braak stage. However, regions of study should be selected carefully.
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