Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5–90 years Joel Simrén, 1,2 Ulf Andreasson, 1,2 Johan Gobom, 1,2 Marc Suarez Calvet, 3,4,5,6 Barbara Borroni, 7 Christopher Gillberg, 8 Lars Nyberg, 9,10,11 Roberta Ghidoni, 12 Elisabeth Fernell, 8 Mats Johnson, 8 Herman Depypere, 13 Caroline Hansson, 1,14 Ingibjörg H. Jonsdottir, 14,15 Henrik Zetterberg 1,2,16,17,18 and Kaj Blennow 1,2 The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has gener- ated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cere- brospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenera- tive diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5–90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95 th percentile in each age category): 5–17 years = 7 pg/mL; 18–50 years = 10 pg/mL; 51–60 years = 15 pg/mL; 61–70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice. 1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden 2 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 43180 Gothenburg, Sweden 3 Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, 08005 Barcelona, Spain 4 IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain 5 Servei de Neurologia, Hospital del Mar, 08003 Barcelona, Spain 6 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), 08003 Madrid, Spain 7 Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, 25125 Brescia, Italy 8 Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, 41119 Gothenburg, Sweden 9 Department of Integrative Medical Biology, Umeå University, 90736 Umeå, Sweden 10 Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90736 Umeå, Sweden 11 Department of Radiation Sciences, Umeå University, 90185 Umeå, Sweden 12 Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy 13 Department of Gynecology, Ghent University Hospital, B-9820 Ghent, Belgium 14 The Institute of Stress Medicine, Region of Västra Götaland, 41319 Gothenburg, Sweden 15 School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41319 Gothenburg, Sweden Received February 15, 2022. Revised May 05, 2022. Accepted June 30, 2022. Advance access publication July 4, 2022 © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. BBR AIN COMMUNICATIONS AIN COMMUNICATIONS https://doi.org/10.1093/braincomms/fcac174 BRAIN COMMUNICATIONS 2022: Page 1 of 8 | 1 Downloaded from https://academic.oup.com/braincomms/article/4/4/fcac174/6628649 by guest on 22 July 2022