{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:23:20Z","timestamp":1792887800599,"version":"4.5.0"},"reference-count":71,"publisher":"Walter de Gruyter GmbH","issue":"7","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (<jats:italic>SMN1<\/jats:italic>) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0\u201318 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.<\/jats:p>","DOI":"10.1515\/cclm-2023-1311","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T20:55:38Z","timestamp":1705092938000},"page":"1252-1265","source":"Crossref","is-referenced-by-count":48,"title":["Neurofilament light protein as a biomarker for spinal muscular atrophy: a review and reference ranges"],"prefix":"10.1515","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3480-5136","authenticated-orcid":false,"given":"Sherif","family":"Bayoumy","sequence":"first","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-7445","authenticated-orcid":false,"given":"Inge M.W.","family":"Verberk","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-6384","authenticated-orcid":false,"given":"Lisa","family":"Vermunt","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-4243","authenticated-orcid":false,"given":"Eline","family":"Willemse","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"den Dulk","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3359-1324","authenticated-orcid":false,"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Department of Pediatrics , Erasmus Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-8206","authenticated-orcid":false,"given":"Dasja","family":"Pajkrt","sequence":"additional","affiliation":[{"name":"Organovir Labs, Department of Pediatric Infectious Diseases , Amsterdam University Medical Centers Location Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Nitz","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Medizinische Fakult\u00e4t , Technische Universit\u00e4t Dresden , Dresden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-0767","authenticated-orcid":false,"given":"Johanna M.P.","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Department of Pediatrics , Erasmus Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"van der Post","sequence":"additional","affiliation":[{"name":"Organovir Labs, Department of Pediatric Infectious Diseases , Amsterdam University Medical Centers Location Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Amsterdam Leukodystrophy Center, Department of Child Neurology , Emma Children\u2019s Hospital, Amsterdam University Medical Center, VU University Amsterdam, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"additional","affiliation":[{"name":"Amsterdam Leukodystrophy Center, Department of Child Neurology , Emma Children\u2019s Hospital, Amsterdam University Medical Center, VU University Amsterdam, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms , Amsterdam , The Netherlands"},{"name":"Center for Translational Immunology , University Medical Center Utrecht , Utrecht , The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-9444","authenticated-orcid":false,"given":"Ewout J.N.","family":"Groen","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, Department of Neurology and Neurosurgery , University Medical Center Utrecht , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3486-2824","authenticated-orcid":false,"given":"Victoria","family":"T\u00fcngler","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Medizinische Fakult\u00e4t , Technische Universit\u00e4t Dresden , Dresden , Germany"},{"name":"University Center for Rare Diseases, Medizinische Fakult\u00e4t Carl Gustav Carus , Technische Universit\u00e4t Dresden , Dresden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine , Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"2024112515323886237_j_cclm-2023-1311_ref_001","doi-asserted-by":"crossref","unstructured":"Verhaart, IEC, Robertson, A, Wilson, IJ, Aartsma-Rus, A, Cameron, S, Jones, CC, et al.. Prevalence, incidence and carrier frequency of 5q\u2013linked spinal muscular atrophy\u00a0\u2013 a literature review. Orphanet J Rare Dis 2017;12:124. https:\/\/doi.org\/10.1186\/s13023-017-0671-8.","DOI":"10.1186\/s13023-017-0671-8"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_002","doi-asserted-by":"crossref","unstructured":"Lally, C, Jones, C, Farwell, W, Reyna, SP, Cook, SF, Flanders, WD. Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States. Orphanet J Rare Dis 2017;12:175. https:\/\/doi.org\/10.1186\/s13023-017-0724-z.","DOI":"10.1186\/s13023-017-0724-z"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_003","doi-asserted-by":"crossref","unstructured":"Groen, EJN, Talbot, K, Gillingwater, TH. Advances in therapy for spinal muscular atrophy: promises and challenges. Nat Rev Neurol 2018;14:214\u201324. https:\/\/doi.org\/10.1038\/nrneurol.2018.4.","DOI":"10.1038\/nrneurol.2018.4"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_004","doi-asserted-by":"crossref","unstructured":"Lefebvre, S, B\u00fcrglen, L, Reboullet, S, Clermont, O, Burlet, P, Viollet, L, et al.. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995;80:155\u201365. https:\/\/doi.org\/10.1016\/0092-8674(95)90460-3.","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_005","doi-asserted-by":"crossref","unstructured":"Lorson, CL, Hahnen, E, Androphy, EJ, Wirth, B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A 1999;96:6307\u201311. https:\/\/doi.org\/10.1073\/pnas.96.11.6307.","DOI":"10.1073\/pnas.96.11.6307"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_006","doi-asserted-by":"crossref","unstructured":"Monani, UR, Lorson, CL, Parsons, DW, Prior, TW, Androphy, EJ, Burghes, AHM, et al.. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 1999;8:1177\u201383. https:\/\/doi.org\/10.1093\/hmg\/8.7.1177.","DOI":"10.1093\/hmg\/8.7.1177"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_007","doi-asserted-by":"crossref","unstructured":"Munsat, TL, Davies, KE. International SMA consortium meeting. (26\u201328 June 1992, Bonn, Germany). Neuromuscul Disord 1992;2:423\u20138. https:\/\/doi.org\/10.1016\/s0960-8966(06)80015-5.","DOI":"10.1016\/S0960-8966(06)80015-5"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_008","doi-asserted-by":"crossref","unstructured":"Wijngaarde, CA, Stam, M, Otto, LAM, Bartels, B, Asselman, F-L, van Eijk, RPA, et al.. Muscle strength and motor function in adolescents and adults with spinal muscular atrophy. Neurology 2020;95:e1988\u20138. https:\/\/doi.org\/10.1212\/wnl.0000000000010540.","DOI":"10.1212\/WNL.0000000000010540"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_009","doi-asserted-by":"crossref","unstructured":"Chaytow, H, Faller, KME, Huang, Y-T, Gillingwater, TH. Spinal muscular atrophy: from approved therapies to future therapeutic targets for personalized medicine. Cell Rep Med 2021;2:100346. https:\/\/doi.org\/10.1016\/j.xcrm.2021.100346.","DOI":"10.1016\/j.xcrm.2021.100346"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_010","doi-asserted-by":"crossref","unstructured":"Ratni, H, Ebeling, M, Baird, J, Bendels, S, Bylund, J, Chen, KS, et al.. Discovery of risdiplam, a selective survival of motor neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J Med Chem 2018;61:6501\u201317. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b00741.","DOI":"10.1021\/acs.jmedchem.8b00741"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_011","doi-asserted-by":"crossref","unstructured":"Wurster, CD, Ludolph, AC. Nusinersen for spinal muscular atrophy. Ther Adv Neurol Disord 2018;11. https:\/\/doi.org\/10.1177\/1756285618754459.","DOI":"10.1177\/1756285618754459"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_012","doi-asserted-by":"crossref","unstructured":"Lee, BH, Collins, E, Lewis, L, Guntrum, D, Eichinger, K, Voter, K, et al.. Combination therapy with nusinersen and AVXS-101 in SMA type 1. Neurology 2019;93:640\u20131. https:\/\/doi.org\/10.1212\/wnl.0000000000008207.","DOI":"10.1212\/WNL.0000000000008207"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_013","doi-asserted-by":"crossref","unstructured":"Dangouloff, T, Botty, C, Beaudart, C, Servais, L, Hiligsmann, M. Systematic literature review of the economic burden of spinal muscular atrophy and economic evaluations of treatments. Orphanet J Rare Dis 2021;16:47. https:\/\/doi.org\/10.1186\/s13023-021-01695-7.","DOI":"10.1186\/s13023-021-01695-7"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_014","doi-asserted-by":"crossref","unstructured":"Kolb, SJ, Coffey, CS, Yankey, JW, Krosschell, K, Arnold, WD, Rutkove, SB, et al.. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol 2017;82:883\u201391. https:\/\/doi.org\/10.1002\/ana.25101.","DOI":"10.1002\/ana.25101"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_015","doi-asserted-by":"crossref","unstructured":"Pino, MG, Rich, KA, Kolb, SJ. Update on biomarkers in spinal muscular atrophy. Biomark Insights 2021;16:11772719211035643. https:\/\/doi.org\/10.1177\/11772719211035643.","DOI":"10.1177\/11772719211035643"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_016","doi-asserted-by":"crossref","unstructured":"Finkel, R, Bertini, E, Muntoni, F, Mercuri, E. 209th ENMC international workshop: outcome measures and clinical trial readiness in spinal muscular atrophy 7\u20139 November 2014, Heemskerk, The Netherlands. Neuromuscul Disord 2015;25:593\u2013602. https:\/\/doi.org\/10.1016\/j.nmd.2015.04.009.","DOI":"10.1016\/j.nmd.2015.04.009"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_017","doi-asserted-by":"crossref","unstructured":"Lin, C-W, Kalb, SJ, Yeh, W-S. Delay in diagnosis of spinal muscular atrophy: a systematic literature review. Pediatr Neurol 2015;53:293\u2013300. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2015.06.002.","DOI":"10.1016\/j.pediatrneurol.2015.06.002"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_018","doi-asserted-by":"crossref","unstructured":"Alves, CRR, Petrillo, M, Spellman, R, Garner, R, Zhang, R, Kiefer, M, et al.. Implications of circulating neurofilaments for spinal muscular atrophy treatment early in life: a case series. Mol Ther Methods Clin Dev 2021;23:524\u201338. https:\/\/doi.org\/10.1016\/j.omtm.2021.10.011.","DOI":"10.1016\/j.omtm.2021.10.011"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_019","doi-asserted-by":"crossref","unstructured":"Nitz, E, Smitka, M, Schallner, J, Akg\u00fcn, K, Ziemssen, T, von der Hagen, M, et al.. Serum neurofilament light chain in pediatric spinal muscular atrophy patients and healthy children. Ann Clin Transl Neurol 2021;8:2013\u201324. https:\/\/doi.org\/10.1002\/acn3.51449.","DOI":"10.1002\/acn3.51449"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_020","doi-asserted-by":"crossref","unstructured":"Winter, B, Guenther, R, Ludolph, AC, Hermann, A, Otto, M, Wurster, CD. Neurofilaments and tau in CSF in an infant with SMA type 1 treated with nusinersen. J Neurol Neurosurg Psychiatr 2019;90:1068\u20139. https:\/\/doi.org\/10.1136\/jnnp-2018-320033.","DOI":"10.1136\/jnnp-2018-320033"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_021","doi-asserted-by":"crossref","unstructured":"Tozawa, T, Kasai, T, Tatebe, H, Shiomi, K, Nishio, H, Tokuda, T, et al.. Intrathecal nusinersen treatment after ventriculo-peritoneal shunt placement: a case report focusing on the neurofilament light chain in cerebrospinal fluid. Brain Dev 2020;42:311\u20134. https:\/\/doi.org\/10.1016\/j.braindev.2019.12.006.","DOI":"10.1016\/j.braindev.2019.12.006"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_022","doi-asserted-by":"crossref","unstructured":"Faravelli, I, Meneri, M, Saccomanno, D, Velardo, D, Abati, E, Gagliardi, D, et al.. Nusinersen treatment and cerebrospinal fluid neurofilaments: an explorative study on Spinal Muscular Atrophy type 3 patients. J Cell Mol Med 2020;24:3034\u20139. https:\/\/doi.org\/10.1111\/jcmm.14939.","DOI":"10.1111\/jcmm.14939"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_023","doi-asserted-by":"crossref","unstructured":"Olsson, B, Alberg, L, Cullen, NC, Michael, E, Wahlgren, L, Kroksmark, AK, et al.. NFL is a marker of treatment response in children with SMA treated with nusinersen. J Neurol 2019;266:2129\u201336. https:\/\/doi.org\/10.1007\/s00415-019-09389-8.","DOI":"10.1007\/s00415-019-09389-8"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_024","doi-asserted-by":"crossref","unstructured":"Moher, D, Liberati, A, Tetzlaff, J, Altman, DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. https:\/\/doi.org\/10.1371\/journal.pmed.1000097.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_025","doi-asserted-by":"crossref","unstructured":"Sofou, K, Shahim, P, Tulinius, M, Blennow, K, Zetterberg, H, Mattsson, N, et al.. Cerebrospinal fluid neurofilament light is associated with survival in mitochondrial disease patients. Mitochondrion 2019;46:228\u201335. https:\/\/doi.org\/10.1016\/j.mito.2018.07.002.","DOI":"10.1016\/j.mito.2018.07.002"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_026","doi-asserted-by":"crossref","unstructured":"Beerepoot, S, Heijst, H, Roos, B, Wamelink, MMC, Boelens, JJ, Lindemans, CA, et al.. Neurofilament light chain and glial fibrillary acidic protein levels in metachromatic leukodystrophy. Brain 2022;145:105\u201318. https:\/\/doi.org\/10.1093\/brain\/awab304.","DOI":"10.1093\/brain\/awab304"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_027","doi-asserted-by":"crossref","unstructured":"Ru, Y, Corado, C, Soon, RKJr, Melton, AC, Harris, A, Yu, GK, et al.. Neurofilament light is a treatment-responsive biomarker in CLN2 disease. Ann Clin Transl Neurol 2019;6:2437\u201347. https:\/\/doi.org\/10.1002\/acn3.50942.","DOI":"10.1002\/acn3.50942"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_028","doi-asserted-by":"crossref","unstructured":"van der Vuurst de Vries, RM, Wong, YYM, Mescheriakova, JY, van Pelt, ED, Runia, TF, Jafari, N, et al.. High neurofilament levels are associated with clinically definite multiple sclerosis in children and adults with clinically isolated syndrome. Mult Scler J 2018;25:958\u201367. https:\/\/doi.org\/10.1177\/1352458518775303.","DOI":"10.1177\/1352458518775303"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_029","doi-asserted-by":"crossref","unstructured":"Toorell, H, Zetterberg, H, Blennow, K, S\u00e4vman, K, Hagberg, H. Increase of neuronal injury markers Tau and neurofilament light proteins in umbilical blood after intrapartum asphyxia. J Matern Fetal Neonatal Med 2018;31:2468\u201372. https:\/\/doi.org\/10.1080\/14767058.2017.1344964.","DOI":"10.1080\/14767058.2017.1344964"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_030","doi-asserted-by":"crossref","unstructured":"Wong, YYM, Bruijstens, AL, Barro, C, Michalak, Z, Melief, MJ, Wierenga, AF, et al.. Serum neurofilament light chain in pediatric MS and other acquired demyelinating syndromes. Neurology 2019;93:e968\u201374. https:\/\/doi.org\/10.1212\/wnl.0000000000008057.","DOI":"10.1212\/WNL.0000000000008057"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_031","doi-asserted-by":"crossref","unstructured":"Kirschen, MP, Yehya, N, Graham, K, Kilbaugh, T, Berg, RA, Topjian, A, et al.. Circulating neurofilament light chain is associated with survival after pediatric cardiac arrest. Pediatr Crit Care Med 2020;21:656\u201361. https:\/\/doi.org\/10.1097\/pcc.0000000000002294.","DOI":"10.1097\/PCC.0000000000002294"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_032","doi-asserted-by":"crossref","unstructured":"Dang Do, AN, Sinaii, N, Masvekar, RR, Baker, EH, Thurm, AE, Soldatos, AG, et al.. Neurofilament light chain levels correlate with clinical measures in CLN3 disease. Genet Med 2021;23:751\u20137. https:\/\/doi.org\/10.1038\/s41436-020-01035-3.","DOI":"10.1038\/s41436-020-01035-3"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_033","doi-asserted-by":"crossref","unstructured":"Anzalone, AJ, Turner, SM, Baleztena, AC, McGuffin, T, Creed, K, Jeromin, A, et al.. Blood biomarkers of sports-related concussion in pediatric athletes. Clin J Sport Med 2021;31:250\u20136. https:\/\/doi.org\/10.1097\/jsm.0000000000000735.","DOI":"10.1097\/JSM.0000000000000735"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_034","doi-asserted-by":"crossref","unstructured":"Vermunt, L, Otte, M, Verberk, IMW, Killestein, J, Lemstra, AW, van der Flier, WM, et al.. Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface. Ann Clin Transl Neurol 2022;9:1832\u20137. https:\/\/doi.org\/10.1002\/acn3.51676.","DOI":"10.1002\/acn3.51676"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_035","doi-asserted-by":"crossref","unstructured":"van der Post, J, van Genderen, JG, Heijst, JA, Blokhuis, C, Teunissen, CE, Pajkrt, D. Plasma neurofilament light is not associated with ongoing neuroaxonal injury or cognitive decline in perinatally HIV infected adolescents: a brief report. Viruses 2022;14:671. https:\/\/doi.org\/10.3390\/v14040671.","DOI":"10.3390\/v14040671"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_036","doi-asserted-by":"crossref","unstructured":"Mackenbach, MJ, Willemse, EAJ, van den Dorpel, JJA, van der Beek, N, D\u00edaz-Manera, J, Rizopoulos, D, et al.. Neurofilament light and its association with CNS involvement in patients with classic infantile Pompe disease. Neurology 2023;101:e594-601. https:\/\/doi.org\/10.1212\/wnl.0000000000207482.","DOI":"10.1212\/WNL.0000000000207482"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_037","unstructured":"UMC NlA. NfL interface for physicians; 2022. Available from: https:\/\/mybiomarkers.shinyapps.io\/Neurofilament\/."},{"key":"2024112515323886237_j_cclm-2023-1311_ref_038","doi-asserted-by":"crossref","unstructured":"Wickham, Averick, M, Bryan, J, Chang, W, McGowan, L, Fran\u00e7ois, R, et al.. Welcome to the tidyverse. J Open Source Softw 2019;4:1686. https:\/\/doi.org\/10.21105\/joss.01686.","DOI":"10.21105\/joss.01686"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_039","doi-asserted-by":"crossref","unstructured":"Bates, D, M\u00e4chler, M, Bolker, B, Walker, S. Fitting linear mixed-effects models Usinglme4. J Stat Software 2015;67:1\u201348. https:\/\/doi.org\/10.18637\/jss.v067.i01.","DOI":"10.18637\/jss.v067.i01"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_040","doi-asserted-by":"crossref","unstructured":"Bakdash, JZ, Marusich, LR. Repeated measures correlation. Front Psychol 2017;8. https:\/\/doi.org\/10.3389\/fpsyg.2017.00456.","DOI":"10.3389\/fpsyg.2017.00456"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_041","doi-asserted-by":"crossref","unstructured":"Valero-Mora, PM. ggplot2: elegant graphics for data analysis. J Stat Software 2010;35:1\u20133. https:\/\/doi.org\/10.18637\/jss.v035.b01.","DOI":"10.18637\/jss.v035.b01"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_042","doi-asserted-by":"crossref","unstructured":"Khalil, M, Teunissen, CE, Otto, M, Piehl, F, Sormani, MP, Gattringer, T, et al.. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 2018;14:577\u201389. https:\/\/doi.org\/10.1038\/s41582-018-0058-z.","DOI":"10.1038\/s41582-018-0058-z"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_043","doi-asserted-by":"crossref","unstructured":"Bridel, C, van Wieringen, WN, Zetterberg, H, Tijms, BM, Teunissen, CE, Alvarez-Cerme\u00f1o, JC, et al.. Diagnostic value of cerebrospinal fluid neurofilament light protein in Neurology: a systematic review and meta-analysis. JAMA Neurol 2019;76:1035\u201348. https:\/\/doi.org\/10.1001\/jamaneurol.2019.1534.","DOI":"10.1001\/jamaneurol.2019.1534"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_044","doi-asserted-by":"crossref","unstructured":"Yuan, A, Rao, MV, Veeranna, Nixon, RA. Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol 2017;9. https:\/\/doi.org\/10.1101\/cshperspect.a018309.","DOI":"10.1101\/cshperspect.a018309"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_045","doi-asserted-by":"crossref","unstructured":"Gafson, AR, Barth\u00e9lemy, NR, Bomont, P, Carare, RO, Durham, HD, Julien, JP, et al.. Neurofilaments: neurobiological foundations for biomarker applications. Brain 2020;143:1975\u201398. https:\/\/doi.org\/10.1093\/brain\/awaa098.","DOI":"10.1093\/brain\/awaa098"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_046","doi-asserted-by":"crossref","unstructured":"Yuan, A, Sershen, H, Veeranna, Basavarajappa, BS, Kumar, A, Hashim, A, et al.. Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in\u00a0vivo. Mol Psychiatry 2015;20:986\u201394. https:\/\/doi.org\/10.1038\/mp.2015.45.","DOI":"10.1038\/mp.2015.45"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_047","doi-asserted-by":"crossref","unstructured":"Budelier, MM, He, Y, Barthelemy, NR, Jiang, H, Li, Y, Park, E, et al.. A map of neurofilament light chain species in brain and cerebrospinal fluid and alterations in Alzheimer\u2019s disease. Brain Commun 2022;4. https:\/\/doi.org\/10.1093\/braincomms\/fcac045.","DOI":"10.1093\/braincomms\/fcac045"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_048","doi-asserted-by":"crossref","unstructured":"Altick, AL, Baryshnikova, LM, Vu, TQ, von Bartheld, CS. Quantitative analysis of multivesicular bodies (MVBs) in the hypoglossal nerve: evidence that neurotrophic factors do not use MVBs for retrograde axonal transport. J Comp Neurol 2009;514:641\u201357. https:\/\/doi.org\/10.1002\/cne.22047.","DOI":"10.1002\/cne.22047"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_049","doi-asserted-by":"crossref","unstructured":"Nixon, RA. Autophagy in neurodegenerative disease: friend, foe or turncoat? Trends Neurosci 2006;29:528\u201335. https:\/\/doi.org\/10.1016\/j.tins.2006.07.003.","DOI":"10.1016\/j.tins.2006.07.003"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_050","doi-asserted-by":"crossref","unstructured":"Alagaratnam, J, von Widekind, S, De Francesco, D, Underwood, J, Edison, P, Winston, A, et al.. Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis. BMJ Neurol Open 2021;3:e000143. https:\/\/doi.org\/10.1136\/bmjno-2021-000143.","DOI":"10.1136\/bmjno-2021-000143"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_051","doi-asserted-by":"crossref","unstructured":"Kuhle, J, Gaiottino, J, Leppert, D, Petzold, A, Bestwick, JP, Malaspina, A, et al.. Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome. J Neurol Neurosurg Psychiatry 2015;86:273\u20139. https:\/\/doi.org\/10.1136\/jnnp-2013-307454.","DOI":"10.1136\/jnnp-2013-307454"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_052","doi-asserted-by":"crossref","unstructured":"Weydt, P, Oeckl, P, Huss, A, M\u00fcller, K, Volk, AE, Kuhle, J, et al.. Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol 2016;79:152\u20138. https:\/\/doi.org\/10.1002\/ana.24552.","DOI":"10.1002\/ana.24552"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_053","doi-asserted-by":"crossref","unstructured":"Piehl, F, Kockum, I, Khademi, M, Blennow, K, Lycke, J, Zetterberg, H, et al.. Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod. Mult Scler 2018;24:1046\u201354. https:\/\/doi.org\/10.1177\/1352458517715132.","DOI":"10.1177\/1352458517715132"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_054","doi-asserted-by":"crossref","unstructured":"Teunissen, CE, Khalil, M. Neurofilaments as biomarkers in multiple sclerosis. Mult Scler 2012;18:552\u20136. https:\/\/doi.org\/10.1177\/1352458512443092.","DOI":"10.1177\/1352458512443092"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_055","doi-asserted-by":"crossref","unstructured":"Reinert, M-C, Benkert, P, Wuerfel, J, Michalak, Z, Ruberte, E, Barro, C, et al.. Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2020;7:e749. https:\/\/doi.org\/10.1212\/nxi.0000000000000749.","DOI":"10.1212\/NXI.0000000000000749"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_056","doi-asserted-by":"crossref","unstructured":"Feneberg, E, Oeckl, P, Steinacker, P, Verde, F, Barro, C, Van Damme, P, et al.. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology 2018;90:e22\u201330. https:\/\/doi.org\/10.1212\/wnl.0000000000004761.","DOI":"10.1212\/WNL.0000000000004761"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_057","doi-asserted-by":"crossref","unstructured":"Zetterberg, H, Skillb\u00e4ck, T, Mattsson, N, Trojanowski, JQ, Portelius, E, Shaw, LM, et al.. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol 2016;73:60\u20137. https:\/\/doi.org\/10.1001\/jamaneurol.2015.3037.","DOI":"10.1001\/jamaneurol.2015.3037"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_058","doi-asserted-by":"crossref","unstructured":"Shahim, P, Gren, M, Liman, V, Andreasson, U, Norgren, N, Tegner, Y, et al.. Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Sci Rep 2016;6:36791. https:\/\/doi.org\/10.1038\/srep36791.","DOI":"10.1038\/srep36791"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_059","doi-asserted-by":"crossref","unstructured":"Sj\u00f6bom, U, Hellstr\u00f6m, W, L\u00f6fqvist, C, Nilsson, AK, Holmstr\u00f6m, G, Pupp, IH, et al.. Analysis of brain injury biomarker neurofilament light and neurodevelopmental outcomes and retinopathy of prematurity among preterm infants. JAMA Netw Open 2021;4:e214138. https:\/\/doi.org\/10.1001\/jamanetworkopen.2021.4138.","DOI":"10.1001\/jamanetworkopen.2021.4138"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_060","doi-asserted-by":"crossref","unstructured":"Goeral, K, Hauck, A, Atkinson, A, Wagner, MB, Pimpel, B, Fuiko, R, et al.. Early life serum neurofilament dynamics predict neurodevelopmental outcome of preterm infants. J Neurol 2021;268:2570\u20137. https:\/\/doi.org\/10.1007\/s00415-021-10429-5.","DOI":"10.1007\/s00415-021-10429-5"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_061","doi-asserted-by":"crossref","unstructured":"Depoorter, A, Neumann, RP, Barro, C, Fisch, U, Weber, P, Kuhle, J, et al.. Neurofilament light chain: blood biomarker of neonatal neuronal injury. Front Neurol 2018;9:984. https:\/\/doi.org\/10.3389\/fneur.2018.00984.","DOI":"10.3389\/fneur.2018.00984"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_062","unstructured":"(EMA) EMA. Letter of Support of neurofilament light in childhood neurological diseases; 2022. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/other\/letter-support-neurofilament-light-childhood-neurological-diseases_en.pdf."},{"key":"2024112515323886237_j_cclm-2023-1311_ref_063","doi-asserted-by":"crossref","unstructured":"Khalil, M, Pirpamer, L, Hofer, E, Voortman, MM, Barro, C, Leppert, D, et al.. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun 2020;11:812. https:\/\/doi.org\/10.1038\/s41467-020-14612-6.","DOI":"10.1038\/s41467-020-14612-6"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_064","doi-asserted-by":"crossref","unstructured":"Benkert, P, Meier, S, Schaedelin, S, Manouchehrinia, A, Yaldizli, \u00d6, Maceski, A, et al.. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol 2022;21:246\u201357. https:\/\/doi.org\/10.1016\/s1474-4422(22)00009-6.","DOI":"10.1016\/S1474-4422(22)00009-6"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_065","doi-asserted-by":"crossref","unstructured":"Abdelhak, A, Petermeier, F, Benkert, P, Sch\u00e4delin, S, Oechtering, J, Maleska Maceski, A, et al.. Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study. Lancet Neurol 2023;22:826\u201333. https:\/\/doi.org\/10.1016\/s1474-4422(23)00210-7.","DOI":"10.1016\/S1474-4422(23)00210-7"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_066","unstructured":"PA, W. Defining, establishing and verifying reference intervals in the clinical laboratory; Approved guideline\u00a0\u2013 3rd ed. CLSI document EP28-A3c. Clinical and Laboratory Standards Institute; 2008."},{"key":"2024112515323886237_j_cclm-2023-1311_ref_067","doi-asserted-by":"crossref","unstructured":"Geis, T, Gutzeit, S, Fouzas, S, Ambrosch, A, Benkert, P, Kuhle, J, et al.. Serum neurofilament light chain (NfL) levels in children with and without neurologic diseases. Eur J Paediatr Neurol 2023;45:9\u201313. https:\/\/doi.org\/10.1016\/j.ejpn.2023.05.003.","DOI":"10.1016\/j.ejpn.2023.05.003"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_068","doi-asserted-by":"crossref","unstructured":"Schj\u00f8rring, ME, Parkner, T, Knudsen, CS, Tybirk, L, Hviid, CVB. Neurofilament light chain: serum reference intervals in Danish children aged 0\u201317 years. Scand J Clin Lab Investig 2023;83:403\u20137. https:\/\/doi.org\/10.1080\/00365513.2023.2251003.","DOI":"10.1080\/00365513.2023.2251003"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_069","doi-asserted-by":"crossref","unstructured":"Wilson, D, Chan, D, Chang, L, Mathis, R, Verberk, I, Montalban, X, et al.. Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury. Clin Chem Lab Med 2024;62:322\u201331. https:\/\/doi.org\/10.1515\/cclm-2023-0518.","DOI":"10.1515\/cclm-2023-0518"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_070","doi-asserted-by":"crossref","unstructured":"Lombardi, V, Carassiti, D, Giovannoni, G, Lu, CH, Adiutori, R, Malaspina, A. The potential of neurofilaments analysis using dry-blood and plasma spots. Sci Rep 2020;10:97. https:\/\/doi.org\/10.1038\/s41598-019-54310-y.","DOI":"10.1038\/s41598-019-54310-y"},{"key":"2024112515323886237_j_cclm-2023-1311_ref_071","doi-asserted-by":"crossref","unstructured":"Andreasson, U, Gobom, J, Delatour, V, Auclair, G, Noam, Y, Lee, S, et al.. Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood. Clin Chem Lab Med 2023;61:1245\u201354. https:\/\/doi.org\/10.1515\/cclm-2022-1181.","DOI":"10.1515\/cclm-2022-1181"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-1311\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-1311\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T15:33:03Z","timestamp":1732548783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-1311\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":71,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,1,15]]},"published-print":{"date-parts":[[2024,6,25]]}},"alternative-id":["10.1515\/cclm-2023-1311"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2023-1311","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}