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Bozzetti et al. Neuroimmunol Neuroinflammation 2021;8:1-13 Neuroimmunology
DOI: 10.20517/2347-8659.2020.26 and Neuroinflammation

Review Open Access

Neurofilament light chain in demyelinating
conditions of the central nervous system: a

promising biomarker

Silvia Bozzetti, Sergio Ferrari, Alberto Gajofatto, Sara Mariotto

Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona 37134, Italy.

Correspondence to: Dr. Sara Mariotto, Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences,
University of Verona, Policlinico GB Rossi, P.le LA Scuro 10, Verona 37134, Italy. E-mail: sara.mariotto@gmail.com
How to cite this article: Bozzetti S, Ferrari S, Gajofatto A, Mariotto S. Neurofilament light chain in demyelinating conditions of
the central nervous system: a promising biomarker. Neuroimmunol Neuroinflammation 2021;8:1-13.
http://dx.doi.org/10.20517/2347-8659.2020.26
Received: 27 Mar 2020 First Decision: 17 Jun 2020 Revised: 23 Jun 2020
Accepted: 16 Jul 2020 Fisrt online: 15 Aug 2020 Published: 21 Mar 2021
Academic Editor: Roberta Magliozzi Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

Abstract
Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to
molecular weight into heavy, intermediate, and light chains. They are released into the interstitial fluid and
cerebrospinal fluid (CSF) as a consequence of axonal damage. In particular, the light chain (NfL) represents
the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with
inflammatory, degenerative, vascular, or traumatic injuries in correlation with clinical and radiological activity.
Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array, which
enables reliable and repeatable measurement of the low NfL concentrations in serum. In particular, CSF and serum
NfL values are strongly correlated in patients with multiple sclerosis (MS) and have been demonstrated to be
increased in patients with MS and clinically isolated syndromes (CIS) in accordance with clinical and radiological
activity. NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment, long-
term outcome, and conversion of CIS to MS. The few available data on patients with other demyelinating diseases
suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in
correlation with attack severity, suggesting that axonal damage may occur in these disorders. We herein report
and discuss published data on the role of NfL as a possible predictor of disease activity, clinical outcome and
treatment response in patients with demyelinating conditions of the central nervous system.

Keywords: Neurofilament light chain, multiple sclerosis, clinically isolated syndromes, radiologically isolated
syndrome, neuromyelitis optica spectrum disorders, myelin oligodendrocyte glycoprotein, aquaporin-4

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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