Plasma neurofilament light chain as a potential biomarker in Charcot-Marie-Tooth disease
Elina Millere
Department of Neurology and Neurosurgery, Children's Clinical University Hospital, Riga, Latvia
Department of Doctoral Studies, Riga Stradins University, Riga, Latvia
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorDmitrijs Rots
Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorJoel Simrén
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorNicholas J. Ashton
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorEinars Kupats
Department of Neurology, Riga East Clinical University Hospital, Riga, Latvia
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorIeva Micule
Clinic of Medical Genetics and Prenatal Diagnostics, Children's Clinical University Hospital, Riga, Latvia
Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorViktorija Priedite
BIOCON Laboratory, Riga, Latvia
Contribution: Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorNatalja Kurjane
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia
Outpatient Service Centre, Pauls Stradins Clinical University Hospital, Riga, Latvia
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorKaj Blennow
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Conceptualization (equal), Investigation (equal), Methodology (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorLinda Gailite
Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorHenrik Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
UK Dementia Research Institute, UCL, London, UK
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Viktorija Kenina
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia
Rare Disease Centre, Riga East Clinical University Hospital, Riga, Latvia
Correspondence
Viktorija Kenina, Department of Biology and Microbiology, Riga Stradins University, Riga LV-1007, Latvia.
Email: [email protected]
Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorElina Millere
Department of Neurology and Neurosurgery, Children's Clinical University Hospital, Riga, Latvia
Department of Doctoral Studies, Riga Stradins University, Riga, Latvia
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorDmitrijs Rots
Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal), Writing - review & editing (equal)
Search for more papers by this authorJoel Simrén
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorNicholas J. Ashton
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorEinars Kupats
Department of Neurology, Riga East Clinical University Hospital, Riga, Latvia
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Writing - review & editing (equal)
Search for more papers by this authorIeva Micule
Clinic of Medical Genetics and Prenatal Diagnostics, Children's Clinical University Hospital, Riga, Latvia
Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorViktorija Priedite
BIOCON Laboratory, Riga, Latvia
Contribution: Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorNatalja Kurjane
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia
Outpatient Service Centre, Pauls Stradins Clinical University Hospital, Riga, Latvia
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorKaj Blennow
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Contribution: Conceptualization (equal), Investigation (equal), Methodology (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorLinda Gailite
Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorHenrik Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK
UK Dementia Research Institute, UCL, London, UK
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Viktorija Kenina
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia
Rare Disease Centre, Riga East Clinical University Hospital, Riga, Latvia
Correspondence
Viktorija Kenina, Department of Biology and Microbiology, Riga Stradins University, Riga LV-1007, Latvia.
Email: [email protected]
Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorHenrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), Alzheimer Drug Discovery Foundation, USA (#201809-2016862), and UK Dementia Research Institute.
Abstract
Background and purpose
Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders.
Methods
Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay.
Results
The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881.
Conclusions
Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.
CONFLICT OF INTEREST
The authors declare no conflict of interest relevant to the submitted study.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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