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Brain communications
Published

CSF neurofilament light chain profiling and quantitation in neurological diseases

Authors

Claire A Leckey, John B Coulton, Tatiana A Giovannucci, Yingxin He, Aram Aslanyan, Rhiannon Laban, Amanda Heslegrave, Ivan Doykov, Francesca Ammoscato, Jeremy Chataway, Floriana De Angelis, Sharmilee Gnanapavan, Lauren M Byrne, Jonathan M Schott, Edward J Wild, Nicolas R Barthelémy, Henrik Zetterberg, Selina Wray, Randall J Bateman, Kevin Mills, Ross W Paterson

Abstract

Brain Commun. 2024 Apr 16;6(3):fcae132. doi: 10.1093/braincomms/fcae132. eCollection 2024.

ABSTRACT

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.

PMID:38707707 | PMC:PMC11069115 | DOI:10.1093/braincomms/fcae132

UK DRI Authors

Amanda Heslegrave

Dr Amanda Heslegrave

Principal Research Fellow

Co-leading the UK DRI Biomarker Factory platform based at UK DRI at UCL

Dr Amanda Heslegrave
Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg