Neurofilaments as biomarkers in neurological disorders

Michael Khalil, Charlotte E. Teunissen, Markus Otto, Fredrik Piehl, Maria Pia Sormani, Thomas Gattringer, Christian Barro, Ludwig Kappos, Manuel Comabella, Franz Fazekas, Axel Petzold, Kaj Blennow, Henrik Zetterberg, Jens Kuhle

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.

Original languageEnglish
Pages (from-to)577-589
Number of pages13
JournalNature Reviews Neurology
Volume14
Issue number10
DOIs
Publication statusPublished - 2018

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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