Leckey, Claire A;
Coulton, John B;
Giovannucci, Tatiana A;
He, Yingxin;
Aslanyan, Aram;
Laban, Rhiannon;
Heslegrave, Amanda;
... Paterson, Ross W; + view all
(2024)
Cerebrospinal fluid neurofilament light chain profiling and quantitation in neurological diseases.
Brain Communications
, 6
(3)
, Article fcae132. 10.1093/braincomms/fcae132.
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Abstract
Neurofilament light chain (NfL) is an established marker of neuroaxonal injury that is elevated in cerebrospinal fluid (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 NfL 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 characterised and quantified NfL species in CSF across neurodegenerative and neuroinflammatory diseases and healthy controls using targeted mass spectrometry. We show that the quantitative immunoprecipitation-tandem mass spectrometry (IP-MS/MS) method developed in this study strongly correlates to single-molecule array (Simoa) 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.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid neurofilament light chain profiling and quantitation in neurological diseases |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/braincomms/fcae132 |
| Publisher version: | http://dx.doi.org/10.1093/braincomms/fcae132 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Neurofilament light chain, mass spectrometry, neurodegenerative diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10191755 |
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