CSF neurofilament light chain reflects corticospinal tract degeneration in ALS
Ricarda A. L. Menke,Elizabeth Gray,Ching-Hua Lu,Jens Kuhle,Kevin Talbot,Andrea Malaspina,Martin R Turner +6 more
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TLDR
Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders and the relationship between these two measures was explored.Abstract:
Objective
Diffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders. The relationship between these two measures was explored.
Methods
CSF and serum NfL concentrations and DTI acquired at 3 Tesla on the same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between NfL and DTI measures of microstructural integrity in major white matter tracts (CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were performed using tract-based spatial statistics.
Results
NfL levels were higher in patients compared to controls. CSF levels correlated with clinical upper motor neuron burden and rate of disease progression. Higher NfL levels were significantly associated with lower DTI fractional anisotropy and increased radial diffusivity in the CSTs of ALS patients, but not in controls.
Interpretation
Elevated CSF and serum NfL is, in part, a result of CST degeneration in ALS. This highlights the wider potential for combining neurochemical and neuroimaging-based biomarkers in neurological disease.read more
Citations
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Journal ArticleDOI
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,Kaj Blennow,Henrik Zetterberg,Jens Kuhle +14 more
TL;DR: How technological advances have enabled the detection of neurofilament proteins in the blood is considered, and how these proteins consequently have the potential to be easily measured biomarkers of neuroaxonal injury in various neurological conditions are discussed.
Journal ArticleDOI
Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis
Claire Bridel,van Wieringen Wn,Henrik Zetterberg,Betty M. Tijms,Charlotte E. Teunissen,José C. Álvarez-Cermeño,Ulf Andreasson,Markus Axelsson,David Bäckström,Ales Bartos,Maria Bjerke,Kaj Blennow,Kaj Blennow,A. Boxer,Lena Brundin,Joachim Burman,Tove Christensen,Lenka Fialová,Lars Forsgren,Jette L. Frederiksen,Magnus Gisslén,Elizabeth Gray,Martin Gunnarsson,Sara Hall,Oskar Hansson,Megan K. Herbert,Joel Jakobsson,Jessen-Krut J,Shorena Janelidze,Gudmundur Johannsson,Gudmundur Johannsson,Michael Jonsson,Ludwig Kappos,Mohsen Khademi,Mohsen Khademi,Michael Khalil,Jens Kuhle,Mikael Landén,Leinonen,Giancarlo Logroscino,Lu Ch,Jan Lycke,Nadia K. Magdalinou,Andrea Malaspina,Niklas Mattsson,Lieke H.H. Meeter,Mehta,Signe Modvig,Tomas Olsson,Tomas Olsson,Ross W. Paterson,Pérez-Santiago J,Fredrik Piehl,Fredrik Piehl,Pijnenburg Yal,Pyykkö Ot,Ragnarsson O,Julio C. Rojas,Romme Christensen J,Sandberg L,Carole Scherling,Jonathan M. Schott,Finn Sellebjerg,Isabella Laura Simone,Tobias Skillbäck,Stilund M,Peter Sundström,Anders Svenningsson,Rosanna Tortelli,Carla Tortorella,Alessandro Trentini,Troiano M,Martin R Turner,van Swieten Jc,Mattias Vågberg,Marcel M. Verbeek,Luisa M. Villar,Pieter Jelle Visser,Pieter Jelle Visser,Anders Wallin,Weiss A,Carsten Wikkelsö,Edward J. Wild +82 more
TL;DR: The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC, and has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
Journal ArticleDOI
Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry
Piotr Lewczuk,Peter Riederer,Sid E. O'Bryant,Marcel M. Verbeek,Bruno Dubois,Pieter Jelle Visser,Kurt A. Jellinger,Sebastiaan Engelborghs,Alfredo Ramirez,Lucilla Parnetti,Clifford R. Jack,Charlotte E. Teunissen,Harald Hampel,Alberto Lleó,Frank Jessen,Lidia Glodzik,Mony J. de Leon,Anne M. Fagan,José Luis Molinuevo,Willemijn J. Jansen,Bengt Winblad,Leslie M. Shaw,Ulf Andreasson,Markus Otto,Brit Mollenhauer,Jens Wiltfang,Martin R Turner,Inga Zerr,Ron Handels,Alexander G. Thompson,Gunilla Johansson,Natalia Ermann,John Q. Trojanowski,Ilker Karaca,Holger Wagner,Patrick Oeckl,Linda J C van Waalwijk van Doorn,Maria Bjerke,Dimitrios Kapogiannis,H. Bea Kuiperij,Lucia Farotti,Yi Li,Brian A. Gordon,Stéphane Epelbaum,Stephanie J.B. Vos,Catharina J.M. Klijn,William E. Van Nostrand,Carolina Minguillon,Matthias Schmitz,Carla Gallo,Andrea Lopez Mato,Florence Thibaut,Simone Lista,Daniel Alcolea,Henrik Zetterberg,Kaj Blennow,Johannes Kornhuber +56 more
TL;DR: In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes the opportunity to extend and update the original paper.
Journal ArticleDOI
Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients
Petra Steinacker,Emily Feneberg,Jochen H. Weishaupt,Johannes Brettschneider,Hayrettin Tumani,Peter M. Andersen,Christine A. F. von Arnim,Sarah Böhm,Jan Kassubek,Christian Kubisch,Christian Kubisch,Dorothée Lulé,Hans-Peter Müller,Rainer Muche,Elmar H. Pinkhardt,Patrick Oeckl,Angela Rosenbohm,Sarah Anderl-Straub,Alexander E Volk,Alexander E Volk,Patrick Weydt,Albert C. Ludolph,Markus Otto +22 more
TL;DR: Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients and their value as prognostic markers should be investigated further.
Journal ArticleDOI
Neurofilament light chain: a biomarker for genetic frontotemporal dementia.
Lieke H.H. Meeter,Elise G.P. Dopper,Lize C. Jiskoot,Raquel Sánchez-Valle,Caroline Graff,Caroline Graff,Luisa Benussi,Roberta Ghidoni,Yolande A.L. Pijnenburg,Barbara Borroni,Daniela Galimberti,Robert Laforce,Mario Masellis,Mario Masellis,Rik Vandenberghe,Isabelle Le Ber,Markus Otto,Rick van Minkelen,Janne M. Papma,Serge A.R.B. Rombouts,Serge A.R.B. Rombouts,Mircea Balasa,Linn Öijerstedt,Linn Öijerstedt,Vesna Jelic,Vesna Jelic,Katrina M. Dick,David M. Cash,David M. Cash,S. Harding,M. Jorge Cardoso,Sebastien Ourselin,Martin N. Rossor,Alessandro Padovani,Elio Scarpini,Chiara Fenoglio,Maria Carmela Tartaglia,Foudil Lamari,Christian Barro,Jens Kuhle,Jonathan D. Rohrer,Charlotte E. Teunissen,John C. van Swieten,John C. van Swieten +43 more
TL;DR: To evaluate cerebrospinal fluid and serum neurofilament light chain levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage.
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