Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.

Chris R Butler, Thomas T Warner, Jonathan D Rohrer, Oliver Bandmann, Henrik Zetterberg, Paul Cook, Lynne Jung, Alison Martin, Fion Bremner, Mario Masellis, Samuel Shribman, Alex Gerhard, James B Rowe, Emmanuel A Tsochatzis, Godfrey T Gillett, Martha S Foiani, Imogen Swift, Amanda Heslegrave, Maggie Burrows, Carolin Heller

Journal: Movement disorders : official journal of the Movement Disorder Society 2021;36(2):503-508

PMID: 33078859

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Abstract

BACKGROUND

Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage.

OBJECTIVE

To identify a biomarker for neurological involvement in WD.

METHODS

Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded.

RESULTS

Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients.

CONCLUSION

NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Address: Department of Clinical and Movement Neurosciences, Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, United Kingdom.; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom.; Department of Neurodegenerative Disease, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, United Kingdom.; Department of Clinical Chemistry, Northern General Hospital, Sheffield, United Kingdom.; UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom.; Department of Clinical Neurosciences, University of Cambridge and Cambridge University Hospitals Trust, Cambridge, United Kingdom.; Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom.; Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg-Essen, Duisburg, Germany.; Department of Brain Sciences, Imperial College London, London, United Kingdom.; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.; Departamento de Neurología, Pontificia Universidad Católica de Chile, Santiago, Chile.; Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.; Neuro-Ophthalmology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.; Department of Clinical Biochemistry, Southampton General Hospital, Southampton, United Kingdom.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom.

DOI: 10.1002/mds.28333

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MeSH Terms: Biomarkers, Copper, Hepatolenticular Degeneration, Humans, Intermediate Filaments, London, Plasma