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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.
Journal article

Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

  • Bridel C Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
  • van Wieringen WN Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, the Netherlands.
  • Zetterberg H Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Tijms BM Department of Neurology and Alzheimer Centre, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
  • Teunissen CE Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
  • Alvarez-Cermeño JC Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Andreasson U Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Axelsson M Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
  • Bäckström DC Third Faculty of Medicine, Department of Neurology, Charles University and General University Hospital, Prague, Czech Republic.
  • Bartos A Department of Biomedical Sciences, Reference Centre for Biological Markers of Dementia (BIODEM), Institute Born Bunge, University of Antwerp, Antwerp, Belgium.
  • Bjerke M Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Blennow K Memory and Aging Center, Department of Neurology, University of California, San Francisco.
  • Boxer A Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
  • Brundin L Department of Neuroscience, Uppsala University, Uppsala, Sweden.
  • Burman J Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Christensen T First Faculty of Medicine, Institute of Medical Biochemistry, Prague, Czech Republic.
  • Fialová L Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
  • Forsgren L Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Frederiksen JL Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Gisslén M Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
  • Gray E Department of Neurology, Faculty of Medicine and Health, Orebro University Hospital, Orebro, Sweden.
  • Gunnarsson M Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
  • Hall S Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
  • Hansson O Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg.
  • Herbert MK Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Jakobsson J Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Jessen-Krut J Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
  • Janelidze S Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg.
  • Johannsson G Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Jonsson M Department of Medicine, University Hospital and University of Basel, Basel, Switzerland.
  • Kappos L Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
  • Khademi M Department of Neurology, Medical University of Graz, Graz, Austria.
  • Khalil M Department of Medicine, University Hospital and University of Basel, Basel, Switzerland.
  • Kuhle J Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Landén M Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio.
  • Leinonen V Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari, Bari, Italy.
  • Logroscino G North-East London and Essex MND Care Centre, Neuroscience and Trauma Centre, Blizard, United Kingdom.
  • Lu CH Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Lycke J Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, Queen Square, London, United Kingdom.
  • Magdalinou NK North-East London and Essex MND Care Centre, Neuroscience and Trauma Centre, Blizard, United Kingdom.
  • Malaspina A Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
  • Mattsson N Alzheimer Centre and Department of Neurology, Erasmus Medical Centre, Rotterdam, the Netherlands.
  • Meeter LH Division of Infectious Diseases, University of California, San Diego.
  • Mehta SR Department of Clinical Immunology, Copenhagen University Hospital, Righospitalet, Copenhagen, Denmark.
  • Modvig S Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
  • Olsson T Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, United Kingdom.
  • Paterson RW Puerto Rico OMICS Centre, University of Puerto Rico Comprehensive Cancer Centre, San Juan.
  • Pérez-Santiago J Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
  • Piehl F Department of Neurology and Alzheimer Centre, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
  • Pijnenburg YAL Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio.
  • Pyykkö OT Department of Neurology, Faculty of Medicine and Health, Orebro University Hospital, Orebro, Sweden.
  • Ragnarsson O Memory and Aging Center, Department of Neurology, University of California, San Francisco.
  • Rojas JC Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Romme Christensen J Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
  • Sandberg L Department of Psychological Science and Neuroscience Program, Belmont University, Nashville, Tennessee.
  • Scherling CS Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, United Kingdom.
  • Schott JM Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Sellebjerg FT Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
  • Simone IL Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Skillbäck T Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Stilund M Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
  • Sundström P Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
  • Svenningsson A Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari, Bari, Italy.
  • Tortelli R Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
  • Tortorella C Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
  • Trentini A Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
  • Troiano M Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
  • Turner MR Alzheimer Centre and Department of Neurology, Erasmus Medical Centre, Rotterdam, the Netherlands.
  • van Swieten JC Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
  • Vågberg M Radboud University Medical Centre, Donders Institute for Brain, Cognition, and Behaviour, Department of Neurology, Nijmegen, the Netherlands.
  • Verbeek MM Immunology Department, Ramon y Cajal University Hospital, Madrid, Spain.
  • Villar LM Department of Neurology and Alzheimer Centre, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
  • Visser PJ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Wallin A Evotec AG, Manfred Eigen Campus, Hamburg, Germany.
  • Weiss A Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Wikkelsø C UCL Institute of Neurology, Queen Square, London, United Kingdom.
  • Wild EJ
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  • 2019-06-18
Published in:
  • JAMA neurology. - 2019
English Importance
Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.


Objectives
To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.


Data Sources
PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.


Study Selection
Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.


Data Extraction and Synthesis
Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.


Main Outcome and Measure
The cNfL levels adjusted for age and sex across diagnoses.


Results
Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.


Conclusions and Relevance
These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/51018
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