International Initiative for Harmonization of Plasma Neurofilament light chain NfL clinical reporting in neurodegenerative diseases

Abstract Background The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut‐points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability. To date, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on COU and cut‐points. This work is an essential step towards consensual harmonization of the clinical use of NfL after CSF and/or blood analysis in various neurological contexts, as advocated by the Alzheimer's Association "Biofluid Based Biomarkers PIA" working group. Method This international project involves 58 clinical laboratories in 16 countries, specializing in the biochemical diagnosis of neurological disorders. By means of a questionnaire, we obtained a description of the COU, pre‐analytical and analytical (biological fluid and method used to quantify NfL) protocols of all the centers involved. Results Of the centers, 42% quantified NfL in CSF, 29% in serum and 28% in plasma, and 1% in dried blood spot. The COUs were as follows: Frontotemporal dementia (FTD, 17%), Alzheimer's disease (AD, 16%), multiple sclerosis (MS, 16%), amyotrophic lateral sclerosis (ALS, 11%), psychiatric syndrome (PS, 10%), Creutzfeldt‐Jakob disease (CJD, 8%), Parkinson's disease (PD, 8%), peripheral neuropathy (PN, 7%) and traumatic brain injury (TBI, 7%). Most centers define pathological cut‐points based on published literature and take age into account (50%). Conclusion Our initial results highlight the state of the art in terms of the clinical use of NfL analysis in CSF and blood in the context of different neurological diseases. We have now defined a coordinator for each COU subgroup and are organizing consensus meetings to harmonize the use and reporting of NfL measurements for the identified clinical applications. The results of these next steps will be presented.

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Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.090643
Primary Topic
Amyotrophic Lateral Sclerosis Research
Type
article
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article

International Initiative for Harmonization of Plasma Neurofilament light chain NfL clinical reporting in neurodegenerative diseases

Barbara Mroszko, Agnieszka Kulczyńska‐Przybik, Lisa Vermunt, Xavier Ayrignac et al.
Alzheimer s & Dementia
Amyotrophic Lateral Sclerosis Research
article

International Initiative for Harmonization of Plasma Neurofilament light chain NfL clinical reporting in neurodegenerative diseases

Barbara Mroszko, Agnieszka Kulczyńska‐Przybik, Lisa Vermunt, Xavier Ayrignac, Koen Poesen, Aurélie Ladang, Dorte Aalund Olsen, Alberto Lleó, Melanie Hart, Lucilla Parnetti, Hayrettin Tumani, Piero Parchi, Kaj Blennow, Sylvain Lehmann, Daniela Terracciano, Élodie Bouaziz-Amar, M Blanc, Mónica A. Pérez, Gustavo Alves Andrade dos Santos, Alicia Algeciras‐Schimnich, Ashvini Keshavan, Kensaku Kasuga, Jens Kühle, Jessica Cusato, Giancarlo Logroscino, Maria Bjerke, Erdinç Dursun, Anthony Fourier, Piotr Lewczuk, Flora Kaczorowski, Marina Herwerth, Muriel Quillard‐Muraine, Isabelle Quadrio, Giulia Musso, Edith Bigot‐Corbel, Susanna Schraen, Magda Tsolaki, Tinatin Chabrashvili, Cheryl L. Wellington, Constance Delaby, Michael Khalil, Tiziana Casoli, Charlotte Elisabeth Teunissen, Duygu Gezen‐Ak, Henrik Zetterberg, Daniela Galimberti, Inês Baldeiras, Brian A. Gordon, Miles Chapman, Claire Paquet, Pèter Köertvelyessy, Daniel Alcolea, Socrates J. Tzartos, Léonor Nogueira, Guido Maria Giuffrè, Raquel Perez Garay, Enrique Rodriguez Borja, Nadine Unterwalder, Jose Yriarte
article en

Abstract

Abstract Background The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut‐points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability. To date, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on COU and cut‐points. This work is an essential step towards consensual harmonization of the clinical use of NfL after CSF and/or blood analysis in various neurological contexts, as advocated by the Alzheimer's Association "Biofluid Based Biomarkers PIA" working group. Method This international project involves 58 clinical laboratories in 16 countries, specializing in the biochemical diagnosis of neurological disorders. By means of a questionnaire, we obtained a description of the COU, pre‐analytical and analytical (biological fluid and method used to quantify NfL) protocols of all the centers involved. Results Of the centers, 42% quantified NfL in CSF, 29% in serum and 28% in plasma, and 1% in dried blood spot. The COUs were as follows: Frontotemporal dementia (FTD, 17%), Alzheimer's disease (AD, 16%), multiple sclerosis (MS, 16%), amyotrophic lateral sclerosis (ALS, 11%), psychiatric syndrome (PS, 10%), Creutzfeldt‐Jakob disease (CJD, 8%), Parkinson's disease (PD, 8%), peripheral neuropathy (PN, 7%) and traumatic brain injury (TBI, 7%). Most centers define pathological cut‐points based on published literature and take age into account (50%). Conclusion Our initial results highlight the state of the art in terms of the clinical use of NfL analysis in CSF and blood in the context of different neurological diseases. We have now defined a coordinator for each COU subgroup and are organizing consensus meetings to harmonize the use and reporting of NfL measurements for the identified clinical applications. The results of these next steps will be presented.

Alzheimer s & DementiaVol. 20(S2)
Vrije Universiteit Brussel (BE), University of Padua (IT), University of British Columbia (CA), Medical University of Białystok (PL), University of Southern Denmark (DK), University of Milan (IT), Universität Ulm (DE), Université de Montpellier (FR), National and Kapodistrian University of Athens (GR), Medical University of Graz (AT), SUNY Upstate Medical University (US), Washington University in St. Louis (US), Université Paris Cité (FR), University of Perugia (IT), AHEPA University Hospital (GR), Hospital de Sant Pau (ES), University Hospital of Basel (CH), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Universitätsklinikum Erlangen (DE), Sorbonne Paris Cité (FR), Hôpital Cochin (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Istanbul University-Cerrahpaşa (TR), Federico II University Hospital (IT), Hôpital Lariboisière (FR), Observatorio de la Inmigración de Tenerife (ES), Mayo Clinic in Arizona (US), UK Dementia Research Institute (GB), Centre Hospitalier Universitaire de Liège (BE), Anhanguera (Brazil) (BR), Hôpital Purpan (FR), National Hospital for Neurology and Neurosurgery (GB), Amsterdam University Medical Centers (NL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), VIB-KU Leuven Center for Brain & Disease Research (BE), Istituto Nazionale di Riposo e Cura per Anziani (IT), University College London (GB), University of Turin (IT), University of Bari Aldo Moro (IT), Université de Rouen Normandie (FR), Istanbul University (TR), Niigata University (JP), University of Coimbra (PT), Charité - Universitätsmedizin Berlin (DE), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), Amsterdam UMC Location Vrije Universiteit Amsterdam (NL), University of Bologna (IT)
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