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

Journal article
Authors Claire Bridel
Wessel N van Wieringen
Henrik Zetterberg
Betty M Tijms
Charlotte E Teunissen
José C Alvarez-Cermeño
Ulf Andreasson
Markus Axelsson
David C Bäckström
Ales Bartos
Maria Bjerke
Adam Boxer
Lou Brundin
Joachim Burman
Tove Christensen
Lenká Fialová
Lars Forsgren
Jette L Frederiksen
Magnus Gisslén
Elizabeth Gray
Martin Gunnarsson
Sara Hall
Oskar Hansson
Megan K Herbert
Joel Jakobsson
Jan Jessen-Krut
Shorena Janelidze
Gudmundur Johannsson
Michael Jonsson
Ludwig Kappos
Mohsen Khademi
Michael Khalil
Jens Kuhle
Mikael Landén
Ville Leinonen
Giancarlo Logroscino
Ching-Hua Lu
Jan Lycke
Nadia K Magdalinou
Andrea Malaspina
Niklas Mattsson
Lieke H Meeter
Sanjay R Mehta
Signe Modvig
Tomas Olsson
Ross W Paterson
Josué Pérez-Santiago
Fredrik Piehl
Yolande A L Pijnenburg
Okko T Pyykkö
Oskar Ragnarsson
Julio C Rojas
Jeppe Romme Christensen
Linda Sandberg
Carole S Scherling
Jonathan M Schott
Finn T Sellebjerg
Isabella L Simone
Tobias Skillbäck
Morten Stilund
Peter Sundström
Anders Svenningsson
Rosanna Tortelli
Carla Tortorella
Alessandro Trentini
Maria Troiano
Martin R Turner
John C van Swieten
Mattias Vågberg
Marcel M Verbeek
Luisa M Villar
Pieter Jelle Visser
Anders Wallin
Andreas Weiss
Carsten Wikkelsø
Edward J Wild
Published in JAMA neurology
Volume 76
Issue 9
Pages 1035-1048
ISSN 2168-6157
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 1035-1048
Language en
Subject categories Psychiatry


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.To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.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.Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.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.The cNfL levels adjusted for age and sex across diagnoses.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.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.

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