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

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Bridel, ClaireVrije Univ Amsterdam Med Ctr, Neurochem Lab, Dept Clin Chem, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands,Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands (author)

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

Article/chapterEnglish2019

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American Medical Association (AMA),2019
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LIBRIS-ID:oai:DiVA.org:uu-395752
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-395752URI
https://doi.org/10.1001/jamaneurol.2019.1534DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-77243URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:141906945URI
https://gup.ub.gu.se/publication/281964URI

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Language:English
Summary in:English

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Subject category:for swepub-publicationtype

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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.

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MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Psykiatri hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Psychiatry hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng

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Skillbäck, TobiasGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xskito (author)
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Wild, Edward J.UCL Inst Neurol, Queen Sq, London, England (author)
Vrije Univ Amsterdam Med Ctr, Neurochem Lab, Dept Clin Chem, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, NetherlandsNeurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands (creator_code:org_t)

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By the author/editor: Bridel, Claire; van Wieringen, W ...; Zetterberg, Henr ...; Tijms, Betty M.; Teunissen, Charl ...; Alvarez-Cermeno, ...; show more...; Andreasson, Ulf, ...; Axelsson, Markus ...; Backstrom, David ...; Bartos, Ales; Bjerke, Maria; Blennow, Kaj, 19 ...; Boxer, Adam; Brundin, Lou; Burman, Joachim, ...; Christensen, Tov ...; Fialova, Lenka; Forsgren, Lars; Frederiksen, Jet ...; Gisslén, Magnus, ...; Gray, Elizabeth; Gunnarsson, Mart ...; Hall, Sara; Hansson, Oskar; Herbert, Megan K ...; Jakobsson, Joel; Jessen-Krut, Jan; Janelidze, Shore ...; Johannsson, Gudm ...; Jonsson, Michael ...; Kappos, Ludwig; Khademi, Mohsen; Khalil, Michael; Kuhle, Jens; Landén, Mikael, ...; Leinonen, Ville; Logroscino, Gian ...; Lu, Ching-Hua; Lycke, Jan, 1956; Magdalinou, Nadi ...; Malaspina, Andre ...; Mattsson, Niklas; Meeter, Lieke H.; Mehta, Sanjay R.; Modvig, Signe; Olsson, Tomas; Paterson, Ross W ...; Perez-Santiago, ...; Piehl, Fredrik; Pijnenburg, Yola ...; Pyykko, Okko T.; Ragnarsson, Oska ...; Rojas, Julio C.; Christensen, Jep ...; Sandberg, Linda; Scherling, Carol ...; Schott, Jonathan ...; Sellebjerg, Finn ...; Simone, Isabella ...; Skillbäck, Tobia ...; Stilund, Morten; Sundstrom, Peter; Svenningsson, An ...; Tortelli, Rosann ...; Tortorella, Carl ...; Trentini, Alessa ...; Troiano, Maria; Turner, Martin R ...; van Swieten, Joh ...; Vagberg, Mattias; Verbeek, Marcel ...; Villar, Luisa M.; Visser, Pieter J ...; Wallin, Anders, ...; Weiss, Andreas; Wikkelsö, Carste ...; Wild, Edward J.; show less...

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