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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\u2013tandem 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae132","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T19:49:21Z","timestamp":1713296961000},"source":"Crossref","is-referenced-by-count":21,"title":["CSF neurofilament light chain profiling and quantitation in neurological diseases"],"prefix":"10.1093","volume":"6","author":[{"given":"Claire A","family":"Leckey","sequence":"first","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"},{"name":"Translational Mass Spectrometry Research Group, UCL Great Ormond Street Hospital Institute of Child Health, University 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Institute at UCL, University College London , London, WC1E 6BT , UK"},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-4553","authenticated-orcid":false,"given":"Yingxin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, Washington University in St Louis , St Louis, MO 63110 , USA"},{"name":"Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis , St Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-6313","authenticated-orcid":false,"given":"Aram","family":"Aslanyan","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Laban","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London, WC1E 6BT , UK"},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London, WC1E 6BT , UK"},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , 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Queen Square Institute of Neurology, University College London , London, WC1B 5EH , UK"},{"name":"National Institute for Health and Care Research, University College London Hospitals, Biomedical Research Centre , London, W1T 7DN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"De Angelis","sequence":"additional","affiliation":[{"name":"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"},{"name":"National Institute for Health and Care Research, University College London Hospitals, Biomedical Research Centre , London, W1T 7DN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmilee","family":"Gnanapavan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Barts Health NHS Trust , London, E1 1BB , 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R","family":"Barthel\u00e9my","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, Washington University in St Louis , St Louis, MO 63110 , USA"},{"name":"Tracy Family SILQ Center, Washington University School of Medicine, Washington University in St Louis , St Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London, WC1E 6BT , UK"},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal, 43180 , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal, 43180 , Sweden"},{"name":"Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay , Hong Kong , China"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI53792 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3062-7050","authenticated-orcid":false,"given":"Selina","family":"Wray","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1702","authenticated-orcid":false,"given":"Randall J","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington 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