Neurofilaments as biomarkers in neurological disorders — towards clinical application

Michael Khalil, Charlotte E. Teunissen, Sylvain Lehmann, Markus Otto, Fredrik Piehl, Tjalf Ziemssen, Stefan Bittner, Maria Pia Sormani, Thomas Gattringer, Samir Abu-Rumeileh, Simon Thebault, Ahmed Abdelhak, Ari Green, Pascal Benkert, Ludwig Kappos, Manuel Comabella, Hayrettin Tumani, Mark S. Freedman, Axel Petzold, Kaj BlennowHenrik Zetterberg, David Leppert, Jens Kuhle

Research output: Contribution to journalReview articleAcademicpeer-review

2 Citations (Scopus)

Abstract

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.
Original languageEnglish
Pages (from-to)269-287
Number of pages19
JournalNature Reviews. Neurology
Volume20
Issue number5
DOIs
Publication statusPublished - 1 May 2024

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