Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.
Ching-Hua Lu,Corrie Macdonald-Wallis,Elizabeth Gray,Neil Pearce,Axel Petzold,Niklas Norgren,Gavin Giovannoni,Pietro Fratta,Katie Sidle,Mark Fish,Richard W. Orrell,Robin S. Howard,Kevin Talbot,Linda Greensmith,Jens Kuhle,Martin R Turner,Andrea Malaspina +16 more
Reads0
Chats0
TLDR
This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls and offers potential for N fL as a pharmacodynamic biomarker in future therapeutic trials.Abstract:
Objective: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). Methods: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale–Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan–Meier analysis. Results: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels ( r = 0.78, p p Conclusion: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. Classification of evidence: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.read more
Citations
More filters
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
Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis.
Giulio Disanto,Christian Barro,Pascal Benkert,Yvonne Naegelin,Sabine Schädelin,Antonella Giardiello,Chiara Zecca,Kaj Blennow,Henrik Zetterberg,David Leppert,Ludwig Kappos,Claudio Gobbi,Jens Kuhle +12 more
TL;DR: The value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS) is explored.
Journal ArticleDOI
Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease
Oliver Preische,Oliver Preische,Stephanie A. Schultz,Anja Apel,Anja Apel,Jens Kuhle,Stephan A. Kaeser,Stephan A. Kaeser,Christian Barro,Susanne Gräber,Elke Kuder-Buletta,Christian LaFougere,Christoph Laske,Christoph Laske,Jonathan Vöglein,Jonathan Vöglein,Johannes Levin,Johannes Levin,Colin L. Masters,Ralph N. Martins,Peter R. Schofield,Peter R. Schofield,Martin N. Rossor,Neill R. Graff-Radford,Stephen Salloway,Bernardino Ghetti,John M. Ringman,James M. Noble,Jasmeer P. Chhatwal,Alison Goate,Tammie L.S. Benzinger,John C. Morris,Randall J. Bateman,Guoqiao Wang,Anne M. Fagan,Eric McDade,Brian A. Gordon,Mathias Jucker,Mathias Jucker +38 more
TL;DR: Serum NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.
Journal ArticleDOI
Neurofilament light chain as a biomarker in neurological disorders
Lorenzo Gaetani,Kaj Blennow,Paolo Calabresi,Massimiliano Di Filippo,Lucilla Parnetti,Henrik Zetterberg +5 more
TL;DR: Evidence that both CSF and blood NfL may serve as diagnostic, prognostic and monitoring biomarkers in neurological diseases is progressively increasing, and N fL is one of the most promising biomarkers to be used in clinical and research setting in the next future.
Journal ArticleDOI
Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa
Jens Kuhle,Christian Barro,Ulf Andreasson,Tobias Derfuss,Raija L.P. Lindberg,Åsa Sandelius,Victor Liman,Niklas Norgren,Kaj Blennow,Henrik Zetterberg +9 more
TL;DR: The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.
References
More filters
Journal ArticleDOI
El Escorial revisited : revised criteria for the diagnosis of amyotrophic lateral sclerosis
TL;DR: The criteria described below represent the result of a three-day workshop, convened at Airlie Conference Center, Warrenton, Virginia on 2–4 April, 1998 by the World Federation of Neurology Research Committee on Motor Neuron Diseases, and are placed on the WFN ALS website.
Journal ArticleDOI
Using the General Linear Mixed Model to Analyse Unbalanced Repeated Measures and Longitudinal Data
TL;DR: The general linear mixed model as discussed by the authors provides a useful approach for analysing a wide variety of data structures which practising statisticians often encounter, such as unbalanced repeated measures data and longitudinal data.
Journal ArticleDOI
A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking
Charlotte E. Teunissen,Axel Petzold,Jeffrey Bennett,Frode S. Berven,Lou Brundin,Manuel Comabella,Diego Franciotta,Jette L. Frederiksen,John O. Fleming,Roberto Furlan,Rogier Q. Hintzen,S Hughes,M. H. Johnson,Eva Krasulova,Jens Kuhle,Maria Chiara Magnone,Cecilia Rajda,Konrad Rejdak,Hollie Schmidt,Vincent Van Pesch,Emmanuelle Waubant,Christian Wolf,Gavin Giovannoni,Bernhard Hemmer,Hayrettin Tumani,Florian Deisenhammer +25 more
TL;DR: A consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network forCSF biomarker research in multiple sclerosis, and focuses on CSf collection procedures, preanalytical factors, and high-quality clinical and paraclinical information.
Journal ArticleDOI
Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss.
TL;DR: This review on the role of neurofilaments as surrogate markers for axonal degeneration in neurological diseases provides a brief background to protein synthesis, assembly, function and degeneration.
Book ChapterDOI
Mixed Models: Using the General Linear Mixed Model to Analyse Unbalanced Repeated Measures and Longitudinal Data
TL;DR: The purpose of this tutorial is to provide readers with a sufficient introduction to the theory to understand the method and a more extensive discussion of model fitting and checking in order to provide guidelines for its use.