Neurofilaments as biomarkers in neurological disorders — towards clinical application

Michael Khalil; Charlotte Teunissen; Sylvain Lehmann; Markus Otto; Fredrik Piehl; Tjalf Ziemssen; Stefan Bittner; Maria Pia Sormani; Thomas Gattringer; Samir Abu-Rumeileh; Simon Thebault; Ahmed Abdelhak; Ari Green; Pascal Benkert; Ludwig Kappos; Manuel Comabella; Hayrettin Tumani; Mark S. Freedman; Axel Petzold; Kaj Blennow; Henrik Zetterberg; David Leppert; Jens Kuhle

doi:10.1038/s41582-024-00955-x

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Neurofilaments as biomarkers in neurological disorders — towards clinical application

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Neurofilaments as biomarkers in neurological disorders — towards clinical application

Michael Khalil, Charlotte Teunissen, Sylvain Lehmann, Markus Otto, Fredrik Piehl, Tjalf Ziemssen, Stefan Bittner, Maria Pia Sormani, Thomas Gattringer, Samir Abu-Rumeileh, …

Nature Reviews Neurology, Vol.20(5), pp.269-287

12/04/2024

DOI: https://doi.org/10.1038/s41582-024-00955-x

Résumé

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

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Titre: Neurofilaments as biomarkers in neurological disorders — towards clinical application
Créateurs - sans rôle: Michael Khalil - Medical University of Graz
Charlotte Teunissen - Amsterdam University Medical Centers
Sylvain Lehmann - Université de Montpellier, Institut des Neurosciences de Montpellier - INM
Markus Otto - Martin Luther University Halle-Wittenberg
Fredrik Piehl - Karolinska Institutet
Tjalf Ziemssen - Technische Universität Dresden
Stefan Bittner - Johannes Gutenberg University Mainz
Maria Pia Sormani - University of Genoa
Thomas Gattringer - Medical University of Graz
Samir Abu-Rumeileh - Martin Luther University Halle-Wittenberg
Simon Thebault - University of Pennsylvania
Ahmed Abdelhak - University of California, San Francisco
Ari Green - University of California, San Francisco
Pascal Benkert - University Hospital of Basel
Ludwig Kappos - University Hospital of Basel
Manuel Comabella - Universitat Autònoma de Barcelona
Hayrettin Tumani - University Hospital Ulm
Mark S. Freedman - University of Ottawa
Axel Petzold - National Hospital for Neurology and Neurosurgery
Kaj Blennow - Sorbonne Université
Henrik Zetterberg - University of Gothenburg
David Leppert - University Hospital of Basel
Jens Kuhle - University Hospital of Basel
Détails de publication: Nature Reviews Neurology, Vol.20(5), pp.269-287
Note de subvention: C.E.T.’s research is supported by the European Commission (Marie Curie International Training Network, grant agreement No. 860197 (MIRIADE), Innovative Medicines Initiatives 3TR (Horizon 2020, grant No. 831434), European Platform for Neurodegenerative Diseases (IMI 2 Joint Undertaking (JU), grant No. 101034344) and European Union Joint Programme – Neurodegenerative Disease Research (JPND; bPRIDE), National MS Society (Progressive MS alliance), Alzheimer Association, Health Holland, the Dutch Research Council (ZonMw), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, and Alzheimer Netherlands. C.T.E. is a recipient of ABOARD, which is a public–private partnership receiving funding from ZonMw (#73305095007) and Health Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). C.E.T. is recipient of TAP-dementia, a ZonMw-funded project (#10510032120003) in the context of the Dutch National Dementia Strategy. S.L. is supported by the Fondation pour la Recherche Médicale (FRM), the Claude Pompidou Foundation, H2020 Marie Skłodowska-Curie Actions MIRIADE project, and the European Metrology Programme for Innovation and Research Neuromet2 project. M.O. was supported by the JPND networks Genfi-Prox (01ED2008A) and bPRIDE (01ED2001), the German Federal Ministry of Education and Research (FTLDc 01GI1007A, Moodmarker 01EW200), the EU (MIRIADE 860197, FAIR-PARK II 633190), the German Research Foundation/DFG (SFB1279), the Foundation of the State Baden-Württemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009) and the Thierry Latran Foundation. F.P. is funded by the Swedish MRC (grant no. 2020-02700), the Knut and Alice Wallenberg Foundation, and the Swedish Brain Foundation. S.B. is supported by the Deutsche Forschungsgemeinschaft (DFG, SFB CRC-TR-128 and CRC-TR-355) and the Hermann and Lilly Schilling Foundation. T.G. acknowledges research support from the Austrian Science Fund and the Austrian Neurological Society. S.A.-R. received support from the Medical Faculty of Martin-Luther-University Halle-Wittenberg (Clinician Scientist-Programm No. CS22/06). S.T. is supported by the MS Canada for Postdoctoral Fellowship. H.T. acknowledges research support by DMSG (German Multiple Sclerosis Society), MWK-BW (Ministry of Science, Research and Arts of the State Baden-Württemberg), University of Ulm, and Chemische Fabrik Karl Bucher. A.P. acknowledges support from the National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital and the UK Department of Health. K.B. is supported by the Swedish Research Council (#2017-00915 and #2022-00732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721 and #AF-968270), Hjärnfonden Sweden (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF agreement (#ALFGBG-715986 and #ALFGBG-965240), the JPND (JPND2019-466-236), the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), and the Alzheimer’s Association 2022-2025 Grant (SG-23-1038904 QC). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No. 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 860197 (MIRIADE), the JPND (JPND2021-00694), the National Institute for Health and Care Research UCL Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). D.L. is supported by the International Progressive MS Alliance (grant PA-2002-36227). J.K. is supported by the Swiss MS Society, the Swiss National Research Foundation (320030_189140/1 and 212534/1), the University of Basel and the International Progressive MS Alliance.
Identifiants: 99160552309311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB; Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article
Champs locaux: hal-04799689