Plasma metals as potential biomarkers in dementia: a case–control study in patients with sporadic Alzheimer’s disease

Sporadic Alzheimer’s disease (AD) is a neurodegenerative disorder that causes the most prevalent form of age-related dementia but its pathogenesis remains obscure. Altered regulation of metals, particularly pan-cerebral copper deficiency, and more regionally-localized perturbation of other metals, a...

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Bibliographic Details
Published in:	Biometals 2018-04, Vol.31 (2), p.267-276
Main Authors:	Xu, Jingshu, Church, Stephanie J., Patassini, Stefano, Begley, Paul, Kellett, Katherine A. B., Vardy, Emma R. L. C., Unwin, Richard D., Hooper, Nigel M., Cooper, Garth J. S.
Format:	Article
Language:	eng
Subjects:	Age Alzheimer Disease - blood Alzheimer's disease Biochemistry Biomarkers Biomarkers - blood Biomedical and Life Sciences Brain Brain damage Calcium Calcium - blood Cell Biology Central nervous system Control Copper Copper - blood Correlation analysis Dementia Dementia - blood Dementia disorders Disease control Female Heavy metals Humans Inductively coupled plasma mass spectrometry Iron Iron - blood Life Sciences Magnesium Magnesium - blood Male Males Medicine/Public Health Metal concentrations Metals - blood Microbiology Neurodegenerative diseases Pathogenesis Pharmacology/Toxicology Plant Physiology Potassium Potassium - blood Selenium Selenium - blood Sex Characteristics Sodium Sodium - blood Spectrometry Zinc Zinc - blood
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Summary:	Sporadic Alzheimer’s disease (AD) is a neurodegenerative disorder that causes the most prevalent form of age-related dementia but its pathogenesis remains obscure. Altered regulation of metals, particularly pan-cerebral copper deficiency, and more regionally-localized perturbation of other metals, are prominent in AD brain although data on how these CNS perturbations are reflected in the peripheral bloodstream are inconsistent to date. To assess the potential use of metal dysregulation to generate biomarkers in AD, we performed a case–control study of seven essential metals and selenium, measured by inductively coupled plasma mass-spectrometry, in samples from AD and matched control cases. Metals were sodium, potassium, calcium, magnesium, iron, zinc, and copper. In the whole study-group and in female participants, plasma metal levels did not differ between cases and controls. In males by contrast, there was moderate evidence that zinc levels trended towards increase in AD [10.8 (10.2–11.5)] µmol/L, mean (± 95% CI; P = 0.021) compared with controls [10.2 (9.6–10.4)]. Thus alterations in plasma zinc levels differed between genders in AD. In correlational analysis, there was evidence for an increased number of ‘strong’ metal co-regulations in AD cases and differential co-modulations of metal pairs: copper-sodium ( R control = − 0.03, R AD = 0.65; P = 0.009), and copper-calcium ( R control = − 0.01, R AD = 0.65; P = 0.01) were significant in AD males, potentially consistent with reported evidence for dysregulation of copper in severely damaged brain regions in AD. In conclusion, our data suggest that the measurement of metals co-regulation in plasma may provide a useful representation of those metal perturbations taking place in the AD brain and therefore might be useful as plasma-based biomarkers. Graphical Abstract
ISSN:	0966-0844 1572-8773