Journal article

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

  • Lu CH From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Macdonald-Wallis C From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Gray E From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Pearce N From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Petzold A From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Norgren N From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Giovannoni G From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Fratta P From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Sidle K From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Fish M From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Orrell R From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Howard R From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Talbot K From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Greensmith L From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Kuhle J From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
  • Turner MR From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK. a.malaspina@qmul.ac.uk martin.turner@ndcn.ox.ac.uk.
  • Malaspina A From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK. a.malaspina@qmul.ac.uk martin.turner@ndcn.ox.ac.uk.
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  • 2015-05-03
Published in:
  • Neurology. - 2015
English OBJECTIVE
To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS).


METHODS
Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis.


RESULTS
CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001).


CONCLUSION
Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials.


CLASSIFICATION OF EVIDENCE
This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/247070
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