Isotopic Evidence for Disrupted Copper Metabolism in Amyotrophic Lateral Sclerosis

Redox-active metals are thought to be implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). To address this point, we measured the concentrations of 12 elements and, for the first time, the stable isotope compositions of copper (redox-active) and zinc (redox-inactiv...

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Published in:iScience 2018-08, Vol.6, p.264-271
Main Authors: Sauzéat, Lucie, Bernard, Emilien, Perret-Liaudet, Armand, Quadrio, Isabelle, Vighetto, Alain, Krolak-Salmon, Pierre, Broussolle, Emmanuel, Leblanc, Pascal, Balter, Vincent
Format: Article
Language:English
Subjects:
Biochemistry
Biochemistry, Molecular Biology
Biotechnology
Cell Behavior
Cellular Biology
Clinical Neuroscience
Genetics
Human genetics
Isotope Chemistry
Life Sciences
Neurobiology
Neurons and Cognition
Neuroscience
Nuclear Medicine
Subcellular Processes
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Summary:Redox-active metals are thought to be implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). To address this point, we measured the concentrations of 12 elements and, for the first time, the stable isotope compositions of copper (redox-active) and zinc (redox-inactive) in human cerebrospinal fluids of 31 patients with ALS, 11 age-matched controls (CTRL), and 14 patients with Alzheimer disease. We first show that metal concentrations weakly discriminate patients with ALS from the two other groups. We then report that zinc isotopic compositions are similar in the three groups, but that patients with ALS have significantly 65copper-enriched isotopic compositions relative to CTRL and patients with AD. This result unambiguously demonstrates that copper is implicated in ALS. We suggest that this copper isotopic signature may result from abnormal protein aggregation in the brain parenchyma, and propose that isotopic analysis is a potential tool that may help unraveling the molecular mechanisms at work in ALS. [Display omitted] •Redox-active metals are implicated in ALS through oxidative stress•Concentrations of these metals in CSFs of patients with ALS are non-specific•Copper stable isotope composition in CSFs of patients with ALS are specific•Isotopic balance between CSFs and brain is probably the mechanism Nuclear Medicine; Isotope Chemistry; Neuroscience; Clinical Neuroscience
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2018.07.023