CSF neurofilament light chain profiling and quantitation in neurological diseases.

Autor:	Leckey CA; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.; Translational Mass Spectrometry Research Group, UCL Great Ormond Street Hospital Institute of Child Health, University College London, London, WC1N 1EH, UK.; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK., Coulton JB; Department of Neurology, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.; Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA., Giovannucci TA; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., He Y; Department of Neurology, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.; Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA., Aslanyan A; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Laban R; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Heslegrave A; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Doykov I; Translational Mass Spectrometry Research Group, UCL Great Ormond Street Hospital Institute of Child Health, University College London, London, WC1N 1EH, UK., Ammoscato F; Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Blizard Institute, Centre for Neuroscience, London, E1 2AT, UK., Chataway J; Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1B 5EH, UK.; National Institute for Health and Care Research, University College London Hospitals, Biomedical Research Centre, London, W1T 7DN, UK., De Angelis F; Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1B 5EH, UK.; National Institute for Health and Care Research, University College London Hospitals, Biomedical Research Centre, London, W1T 7DN, UK., Gnanapavan S; Department of Neurology, Barts Health NHS Trust, London, E1 1BB, UK., Byrne LM; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Schott JM; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Wild EJ; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Barthelémy NR; Department of Neurology, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.; Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA., Zetterberg H; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, 43180, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, 43180, Sweden.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI53792, USA., Wray S; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK., Bateman RJ; Department of Neurology, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.; Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA., Mills K; Translational Mass Spectrometry Research Group, UCL Great Ormond Street Hospital Institute of Child Health, University College London, London, WC1N 1EH, UK., Paterson RW; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.; UK Dementia Research Institute at UCL, University College London, London, WC1E 6BT, UK.; Department of Neurology, Darent Valley Hospital, Dartford, Kent, DA2 8DA, UK.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2024 Apr 16; Vol. 6 (3), pp. fcae132. Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).
DOI:	10.1093/braincomms/fcae132
Abstrakt:	Neurofilament light chain is an established marker of neuroaxonal injury that is elevated in CSF and blood across various neurological diseases. It is increasingly used in clinical practice to aid diagnosis and monitor progression and as an outcome measure to assess safety and efficacy of disease-modifying therapies across the clinical translational neuroscience field. Quantitative methods for neurofilament light chain in human biofluids have relied on immunoassays, which have limited capacity to describe the structure of the protein in CSF and how this might vary in different neurodegenerative diseases. In this study, we characterized and quantified neurofilament light chain species in CSF across neurodegenerative and neuroinflammatory diseases and healthy controls using targeted mass spectrometry. We show that the quantitative immunoprecipitation-tandem mass spectrometry method developed in this study strongly correlates to single-molecule array measurements in CSF across the broad spectrum of neurodegenerative diseases and was replicable across mass spectrometry methods and centres. In summary, we have created an accurate and cost-effective assay for measuring a key biomarker in translational neuroscience research and clinical practice, which can be easily multiplexed and translated into clinical laboratories for the screening and monitoring of neurodegenerative disease or acute brain injury. Competing Interests: H.Z. has served at scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). R.J.B. and R.W.P. lead The Neurofilament Light Consortium, an industry academic collaboration that is supported by AbbVie, Bristol Myers Squibb, Biogen and Roche. R.W.P. has received honoraria from GE Healthcare for educational talks, which is used to support academic work. R.J.B. has received research funding from Avid Radiopharmaceuticals, Janssen, Roche/Genentech, Eli Lilly, Eisai, Biogen, AbbVie, Bristol Myers Squibb and Novartis. Washington University and R.J.B. have equity ownership interest in C2N Diagnostics and receive income based on technology (neurofilament light chain assays and materials) licenced by Washington University to C2N Diagnostics. R.J.B. receives income from C2N Diagnostics for serving on the scientific advisory board. R.J.B. serves on the Roche Gantenerumab Steering Committee as an unpaid member. J.C. has received support from the Health Technology Assessment (HTA) Programme (National Institute for Health Research, NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in multiple sclerosis funded by the Multiple Sclerosis Society of Canada. A local principal investigator for commercial trials was funded by Ionis, Novartis and Roche and has taken part in advisory boards/consultancy for Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis and Roche. The MS-SMART trial was funded by the Efficacy and Mechanism Evaluation programme as project number 11/30/11. MS-SMART is an investigator-led project sponsored by the University College London. This independent research is awarded by and funded by the Medical Research Council, the UK MS Society and the National MS Society and is managed by the National Institute for Health Research on behalf of the Medical Research Council–National Institute for Health partnership. Additional support came from the University of Edinburgh, the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London and the National Institute for Health Research Leeds Clinical Research Facility (Dental Translational and Clinical Research Unit). Riluzole was provided without charge by Sanofi-Genzyme who was not involved in either the trial design, running of the trial or analysis. F.D.A. received speaker honoraria from Neurology Academy, Janssen, Merck, Novartis and Sanofi; is on the advisory board for Novartis and Coloplast; has received congress fees from Janssen, Merck, Novartis and Roche; and is a regional coordinator for the Oratorio Hand Trial (Hoffmann-La Roche). The rest of the authors declared no conflicting interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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