TY - JOUR
T1 - Neurofilaments as biomarkers in neurological disorders — towards clinical application
AU - Khalil, Michael
AU - Teunissen, Charlotte E.
AU - Lehmann, Sylvain
AU - Otto, Markus
AU - Piehl, Fredrik
AU - Ziemssen, Tjalf
AU - Bittner, Stefan
AU - Sormani, Maria Pia
AU - Gattringer, Thomas
AU - Abu-Rumeileh, Samir
AU - Thebault, Simon
AU - Abdelhak, Ahmed
AU - Green, Ari
AU - Benkert, Pascal
AU - Kappos, Ludwig
AU - Comabella, Manuel
AU - Tumani, Hayrettin
AU - Freedman, Mark S.
AU - Petzold, Axel
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Leppert, David
AU - Kuhle, Jens
N1 - Publisher Copyright: © Springer Nature Limited 2024.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85190102405&partnerID=8YFLogxK
U2 - 10.1038/s41582-024-00955-x
DO - 10.1038/s41582-024-00955-x
M3 - Review article
C2 - 38609644
SN - 1759-4758
VL - 20
SP - 269
EP - 287
JO - Nature Reviews. Neurology
JF - Nature Reviews. Neurology
IS - 5
ER -