Neurofilaments as biomarkers in neurological disorders - towards clinical application

Research output: Contribution to journalReview articleContributedpeer-review


  • Michael Khalil - , Medical University of Graz (Author)
  • Charlotte E Teunissen - , Amsterdam University Medical Centers (UMC), Vrije Universiteit Amsterdam (VU) (Author)
  • Sylvain Lehmann - , CHU Montpellier, University of Montpellier (Author)
  • Markus Otto - , Martin Luther University Halle-Wittenberg (Author)
  • Fredrik Piehl - , Karolinska Institutet (Author)
  • Tjalf Ziemssen - , Department of Neurology (Author)
  • Stefan Bittner - , University Medical Center Mainz (Author)
  • Maria Pia Sormani - , IRCCS Ospedale Policlinico San Martino, Genova, Italy. (Author)
  • Thomas Gattringer - , Medical University of Graz (Author)
  • Samir Abu-Rumeileh - , Martin Luther University Halle-Wittenberg (Author)
  • Simon Thebault - , University of Pennsylvania Perelman School of Medicine (Author)
  • Ahmed Abdelhak - , UCSF Weill Institute for Neuroscience (Author)
  • Ari Green - , UCSF Weill Institute for Neuroscience (Author)
  • Pascal Benkert - , University Hospital Basel (Author)
  • Ludwig Kappos - , University Hospital Basel (Author)
  • Manuel Comabella - , Vall d'Hebron University Hospital , Autonomous University of Barcelona (Author)
  • Hayrettin Tumani - , Ulm University Medical Center (Author)
  • Mark S Freedman - , Ottawa Hospital Research Institute (Author)
  • Axel Petzold - , National Hospital for Neurology and Neurosurgery, University College London (Author)
  • Kaj Blennow - , University of Science and Technology of China (USTC), The First Affiliated Hospital of USTC China (Author)
  • Henrik Zetterberg - , University of Wisconsin-Madison (Author)
  • David Leppert - , University Hospital Basel (Author)
  • Jens Kuhle - , University Hospital Basel (Author)


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
Issue number5
Early online date12 Apr 2024
Publication statusPublished - May 2024

External IDs

Scopus 85190102405



  • Intermediate Filaments/metabolism, Nervous System Diseases/diagnosis, Humans, Biomarkers/metabolism, Neurofilament Proteins/blood