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Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis

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Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.

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Acknowledgments

Per M. Roos initiated the study and performed the clinical and electromyographical examinations, collected the samples and prepared the first draft of the manuscript. Tore Syversen supervised the laboratory work. We are grateful to Lars Evje, Syverin Lierhagen and Kristin Gellein for performing the metal analyses. Statistician Jakob Bergstrom is acknowledged for his contributions in preparation and completion of the manuscript and for the statistical analyses which were made during his employment at The Medical Statistics Unit, Department of Learning, Informatics, Management & Ethics (LIME), Karolinska Institutet, Stockholm, Sweden. Funding from Martin Rinds foundation and Karolinska Institutet research funds are gratefully acknowledged. Skilful secretarial assistance by Ms. Mona Nyang is noted.

Conflicts of interest

No conflicts of interest have been reported by the authors.

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Authors and Affiliations

  1. Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 17177, Stockholm, Sweden

    Per M. Roos & Monica Nordberg

  2. Faculty of Natural Sciences, Uppsala University, Uppsala, Sweden

    Olof Vesterberg

  3. Department of Neurology, Oslo University Hospital, Oslo, Norway

    Per M. Roos

  4. Department of Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway

    Per M. Roos

  5. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

    Tore Syversen

  6. Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway

    Trond Peder Flaten

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  1. Per M. Roos
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  2. Olof Vesterberg
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  4. Trond Peder Flaten
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  5. Monica Nordberg
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Correspondence to Per M. Roos.

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Concentrations (micrograms per litre) of metals in CSF and blood plasma and ratios between them. Ratios were calculated by dividing CSF concentrations by blood plasma concentrations (C/B ratios). Mass-spectrometric counts are compared to reference material, and in the lowest range, negative numbers can occur. In case of negative numbers, concentrations have been set to zero. When a division with zero was needed, the actual values were reported. Grey cells represent ALS cases, and white cells represent controls. (PDF 47 kb)

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Roos, P.M., Vesterberg, O., Syversen, T. et al. Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis. Biol Trace Elem Res 151, 159–170 (2013). https://doi.org/10.1007/s12011-012-9547-x

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  • DOI: https://doi.org/10.1007/s12011-012-9547-x

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