Serum Neurofilament Light Chain: A Potential Biomarker for Peripheral Neuropathy

I Putu Eka  Widyadharma; Eric Hartono  Tedyanto

doi:10.33192/Smj.2022.84

Authors

I Putu Eka Widyadharma Department of Neurology, Faculty of Medicine, Universitas Udayana, Bali
Eric Hartono Tedyanto Department of Neurology, Faculty of Medicine, Universitas Udayana, Bali

DOI:

https://doi.org/10.33192/Smj.2022.84

Keywords:

Biomarker, neurofilament light chain, peripheral neuropathy, prognostic

Abstract

In some neurological diseases, advanced examinations can be used as diagnostic tools. Several indicators have also been discovered that can be used to assess the severity of neuronal damage and neurological disease progression. Neurofilament light chain (NfL) is a cytoskeleton protein that makes up the structure of neuron axons and is released when a neuron is injured, allowing it to assess neuronal injury severity. NfL was first used to diagnose central nervous system disorders like dementia, multiple sclerosis, and other neurodegenerative diseases. But, NfL levels have also been elevated in peripheral nervous system disorders, like in several neuropathic conditions, including amyloid neuropathy, HIV-associated neuropathy, diabetic peripheral neuropathy, leprosy neuropathy, and other neuropathy, according to various investigations. Theoretically, all abnormalities induced by axonal injury will increase blood NfL levels, allowing NfL testing to be utilized as a measurement tool. NfL levels can also be a predictive indicator to monitor treatment efficacy and peripheral neuropathy progression.

References

Barro C, Chitnis T, Weiner HL. Blood neurofilament light: a critical review of its application to neurologic disease. Ann Clin Transl Neurol. 2020;7(12):2508-23.

Thebault S, Booth RA, Freedman MS. Blood neurofilament light chain: The neurologist’s troponin? Biomedicines. 2020;8(11):1-11.

Sejbaek T, Mendoza JP, Penner N, Madsen JS, Olsen DA, Illes Z. Comparison of neurofilament light chain results between two independent facilities. BMJ Neurol Open. 2020;2(2):e000063.

Ladang A, Kovacs S, Lengelé L, Locquet M, Reginster JY, Bruyère O, et al. Neurofilament light chain concentration in an aging population. Aging Clin Exp Res. 2022;34(2):331-9.

Bäckström D, Linder J, Jakobson Mo S, Riklund K, Zetterberg H, Blennow K, et al. NfL as a biomarker for neurodegeneration and survival in Parkinson disease. Neurology. 2020;95(7):e827-38.

Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90(8):870-81.

Benn M. Peripheral Neuropathy-Time for Better Biomarkers? Clin Chem. 2020;66(5):638-40.

Remiche G, Kadhim H, Maris C, Mavroudakis N. Peripheral neuropathies, from diagnosis to treatment, review of the literature and lessons from the local experience. Rev Med Brux. 2013;34(4):211-20.

Celikbilek A, Tanik N, Sabah S, Borekci E, Akyol L, Ak H, et al. Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy. Mol Biol Rep. 2014;41(6):4017-22.

Thebault S, Tessier DR, Lee H, Bowman M, Bar-Or A, Arnold DL, et al. High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS. Neurol Neuroimmunol Neuroinflammation. 2019;6(5):e598.

Wilson DH, Rissin DM, Kan CW, Fournier DR, Piech T, Campbell TG, et al. The Simoa HD-1 Analyzer: A Novel Fully Automated Digital Immunoassay Analyzer with Single-Molecule Sensitivity and Multiplexing. J Lab Autom. 2016;21(4):533-47.

Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain. 2003;126(3):590-7.

Kuchel GA, Poon T, Irshad K, Richard C, Julien JP, Cowen T. Decreased neurofilament gene expression is an index of selective axonal hypotrophy in ageing. Neuroreport. 1996;7(8):1353-9.

Perrot R, Berges R, Bocquet A, Eyer J. Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol. 2008;38(1):27-65.

Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857-70.

Landqvist Waldö M, Frizell Santillo A, Passant U, Zetterberg H, Rosengren L, Nilsson C, et al. Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia. BMC Neurol. 2013;13.

Ferreira-Atuesta C, Reyes S, Giovanonni G, Gnanapavan S. The Evolution of Neurofilament Light Chain in Multiple Sclerosis. Front Neurosci. 2021;15:642384.

Sandelius Å, Zetterberg H, Blennow K, Adiutori R, Malaspina A, Laura M, et al. Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology. 2018;90(6):e518-24.

Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions. Front Pain Res. (Lausanne). 2022;3:864910.

Maia LF, Maceski A, Conceição I, Obici L, Magalhães R, Cortese A, et al. Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy. Amyloid. 2020;27(2):97-102.

Kapoor M, Foiani M, Heslegrave A, Zetterberg H, Lunn MP, Malaspina A, et al. Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis. J Peripher Nerv Syst. 2019;24(4):314-9.

Reilly MM, King RHM. Familial Amyloid Polyneuropathy. Brain Pathol. 1993;3(2):165-76.

Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79(6):733-48.

Amruth G, Praveen-kumar S, Nataraju B, Nagaraja BS. HIV associated sensory neuropathy. J Clin Diagn Res. 2014;8(7): MC04-7.

Damian A, Skolasky R, Demsky C, McArthur J, Sacktor N, Zetterberg H, et al. Neurofilament light chain protein levels in HIV positive subjects with neuropathy. Neurology. 2019;92(15).

Gisslén M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, et al. Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. EBioMedicine. 2015;3:135-40.

Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol. 2010;6(12):657–66.

Cavaletti G, Cornblath DR, Merkies ISJ, Postma TJ, Rossi E, Frigeni B, et al. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: From consensus to the first validity and reliability findings. Ann Oncol. 2013;24(2):454-62.

Meregalli C, Fumagalli G, Alberti P, Canta A, Carozzi VA, Chiorazzi A, et al. Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy. Exp Neurol. 2018;307:129-32.

Kim SH, Choi MK, Park NY, Hyun JW, Lee MY, Kim HJ, et al. Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy. Sci Rep. 2020;10(1):7995.

Cai L, Huang J. Neurofilament light chain as a biological marker for multiple sclerosis: A meta-analysis study. Neuropsychiatr Dis Treat. 2018;14:2241-54.

Morgenstern J, Groener JB, Jende JME, Kurz FT, Strom A, Göpfert J, et al. Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy. Diabetologia. 2021;64(12):2843-55.

Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2001;24(8):1448-53.

Sano T, Masuda Y, Yasuno H, Shinozawa T, Watanabe T, Kakehi M. Blood Neurofilament Light Chain as a Potential Biomarker for Central and Peripheral Nervous Toxicity in Rats. Toxicol Sci. 2021;185(1):10-8.

Nascimento OJM. Leprosy neuropathy: Clinical presentations. Arq Neuropsiquiatr. 2013;71(9 B):661-6.

Hassan R, Hui M, Sireesha Y, Afshan J, Meena AK, Uppin MS. Understanding demyelination in leprosy neuropathy: A nerve biopsy analysis. Ann Indian Acad Neurol. 2020;23(6):829-32.

Bennett GJ, Peter CPN. Herpes zoster and postherpetic neuralgia: Past, present and future. Pain Res Manag. 2009;14(4):275-82.

Verde F, Otto M, Silani V. Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Front Neurosci. 2021;15:679199.

Wang Z, Wang R, Li Y, Li M, Zhang Y, Jiang L, et al. Plasma Neurofilament Light Chain as a Predictive Biomarker for Post-stroke Cognitive Impairment: A Prospective Cohort Study. Front Aging Neurosci. 2021;13:631738.