期刊
BRAIN COMMUNICATIONS
卷 4, 期 4, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/braincomms/fcac174
关键词
neurofilament light; plasma; biomarkers; reference limits; clinical chemistry
资金
- Stohne's stiftelse
- Stiftelsen for Gamla Tjanarinnor
- Demensfonden
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]
- AD Strategic Fund
- Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- Olav Thon Foundation
- Erling-Persson Family Foundation
- Hjarnfonden, Sweden [FO2017-0243, FO2019-0228]
- European Union [860197]
- European Union Joint Program for Neurodegenerative Disorders [JPND2021-00694, JPND2019-466-236]
- UK Dementia Research Institute at UCL
- Swedish Alzheimer Foundation [AF-742881]
- ADDF [RDAPB-201809-2016615]
- Swedish government [ALFGBG-715986]
- Swedish County Councils, the Avtal om Lakarutbildning och Forskning agreement [ALFGBG-715986]
- National Institutes of Health [1R01AG068398-01]
- Alzheimer's Association 2021 Zenith Award [ZEN-21-848495]
- Swedish Alzheimer fund Alzheimerfonden [AF-930934]
- Ahlensstiftelsen [213036]
- Stiftelsen GamLa Tjanarinnor
- Knut and Alice Wallenberg (KAW) Foundation
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [948677]
- Instituto de Salud Carlos III [PI19/00155]
- 'la Caixa' Foundation [100010434]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [847648 (LCF/BQ/PR21/11840004)]
- Italian Ministry of Health, Ricerca Corrente
The recent development of a new method to accurately measure neurofilament light in plasma has revealed its potential as a sensitive and robust biomarker for neuroaxonal damage. Efforts are now being made to incorporate plasma neurofilament light into clinical practice and establish reference values to aid interpretation of test results.
The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated 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 cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative 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. Simren et al. report age-stratified cut-offs for plasma neurofilament light, based on a large material of healthy individuals across the ages 5-90 years. The findings will assist clinical implementation of plasma neurofilament light in clinical routine, by simplifying interpretation of concentrations across the lifespan as neurofilament light increases with age.
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