Age-Related Normative Data and Percentile Ranges for Serum Neurofilament Light Chain Levels

Authors

  • Anuschka Silva-Spínola Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-5188-987X
  • Miguel Tábuas-Pereira Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal; Neurology Department, Coimbra University Hospital, ULS Coimbra, Coimbra, Portugal
  • Maria João Leitão Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal
  • Catarina Bernardes Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal; Neurology Department, Coimbra University Hospital, ULS Coimbra, Coimbra, Portugal
  • Marisa Lima Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Center for Research in Neuropsychology and Cognitive Behavioral Intervention (CINEICC), University of Coimbra, Coimbra, Portugal
  • João Durães Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal; Neurology Department, Coimbra University Hospital, ULS Coimbra, Coimbra, Portugal
  • Sandra Freitas Center for Research in Neuropsychology and Cognitive Behavioral Intervention (CINEICC), University of Coimbra, Coimbra, Portugal; Psychological Assessment and Psychometrics Laboratory (PsyAssessmentLab), Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal; Department of Psychology and Education, University of Beira Interior, Covilhã, Portugal
  • Isabel Santana Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal; Neurology Department, Coimbra University Hospital, ULS Coimbra, Coimbra, Portugal
  • Inês Baldeiras Center for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CiBB), University of Coimbra, Coimbra, Portugal; Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal

DOI:

https://doi.org/10.46531/sinapse/AO/150/2025

Keywords:

Biomarkers, Neurodegenerative Diseases

Abstract

Introduction: Blood-based neurofilament light chain (NfL), a neuronal cytoskeleton protein, has proven to be a dynamic and robust biomarker for neurodegeneration. The influence of age on NfL levels has been extensively documented in cerebrospinal fluid studies, with blood quantification showing similar trends. To aid the clinical interpretation of NfL values, it is crucial to establish normal reference intervals through population-specific studies that account for NfL’s dynamic range.

Methods: In this study, we determined reliable age-stratified reference values for serum NfL (sNfL) using the single-molecule array (SiMoA) immunoassay in individuals with no evidence of cognitive impairment according to age- and education-adjusted normative data for the Mini-Mental State Examination (MMSE), recruited from the central region of Portugal, across a broad age range.

Results: Our sample comprised 335 individuals (median age of 53 years, 57% female) aged 20 to 99 years. We found a strong correlation between age and sNfL levels (rho=0.72, p<0.001). Age-stratified reference limits (upper 95th percentile in each decade) were established as follows: 20-30 years= 9.77 pg/mL; 31-40 years= 13.3 pg/mL; 41-50 years= 16.5 pg/mL; 51-60 years= 21.2 pg/mL; 61-70 years= 41.3 pg/mL; 71-80 years= 48.1 pg/mL; 80+ years= 62.5 pg/mL.

Conclusion: These findings provide a unique national normative baseline for the Portuguese population.

Downloads

Download data is not yet available.

References

Zetterberg H. Blood-based biomarkers for Alzheimer’s disease-An update. J Neurosci Methods. 2019;319:2-6. doi:10.1016/j.jneumeth.2018.10.025

Barro C, Chitnis T, Weiner HL. Blood neurofilament light: a critical review of its application to neurologic disease. Ann Clin Transl Neurol. 2020;7:2508-23. doi:10.1002/acn3.51234

Lopes das Neves P, Duraes J, Silva-Spínola A, Lima M, Leitão MJ, Tábuas-Pereira M, et al. Serum Neurofilament Light Chain in the Diagnostic Evaluation of Patients with Cognitive Symptoms in the Neurological Consultation of a Tertiary Center. J Alzheimers Dis. 2023;95:391-7. doi:10.3233/JAD-221208

Vecchio D, Puricelli C, Malucchi S, Virgilio E, Martire S, Perga S, et al. Serum and cerebrospinal fluid neurofilament light chains measured by SIMOA™, Elia™, and Lumipulse™ in multiple sclerosis naive patients. Mult Scler Relat Disord. 2024;82:105412. doi:10.1016/j.msard.2023.105412

Santana I, Duro D, Lemos R, Costa V, Pereira M, Simões MR, Freitas S. Mini-Mental State Examination: Screening and Diagnosis of Cognitive Decline, Using New Normative Data. Acta Med Port. 2016; 29:240-8.

Khalil M, Pingamur 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. doi:10.1038/s41467-020-14612-6

Divo MJ, Martinez CH, Mannino DM. Ageing and the epidemiology of multimorbidity. Eur Respir J. 2014;44:1055-68. doi:10.1183/09031936.00059814

Harp C, Thanei GA, Jia X, Kuhle J, Leppert D, Schaeedlin S, et al. Development of an age-adjusted model for blood neurofilament light chain. Ann Clin Transl Neurol. 2022;9:444-53. doi:10.1002/acn3.51524

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;9:1832-7. doi:10.1002/acn3.51676

Simrén J, Andreasson U, Gobom J, Suarez Calvet M, Borroni B, Gillberg C, et al. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years. Brain Commun. 2022;4(4):fcac174. doi:10.1093/braincomms/fcac174

Fitzgerald KC, Soitchos ES, Smith MD, Lord HN, DuVal A, Mowry EM, et al. Contributors to Serum NFL Levels in People without Neurologic Disease. Ann Neurol. 2022;92:688-98. doi:10.1002/ana.26446

Polymers AA, Helfenstein F, Benkert P, et al. Renal function and body mass index contribute to serum neurofilament light chain levels in elderly patients with atrial fibrillation. Front Neurosci. 2022;16:819010. doi:10.3389/fnins.2022.819010

Downloads

Published

2026-01-04

How to Cite

1.
Silva-Spínola A, Tábuas-Pereira M, Leitão MJ, Bernardes C, Lima M, Durães J, et al. Age-Related Normative Data and Percentile Ranges for Serum Neurofilament Light Chain Levels. Sinapse [Internet]. 2026 Jan. 4 [cited 2026 Jan. 6];25(4):159-63. Available from: https://sinapse.pt/index.php/journal/article/view/150

Issue

Vol. 25 No. 4 (2025): October - December

Section

Original Articles

License

Copyright (c) 2026 Anuschka Spínola, Miguel Tábuas-Pereira, Maria João Leitão, Catarina Bernardes, Marisa Lima, João Durães, Sandra Freitas, Isabel Santana, Inês Baldeiras

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Most read articles by the same author(s)