Observational studyNeurology2020
Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS.
Abstract readMulticenter StudyObservational StudyValidation Study
In one paragraph
Observational study in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed, 5 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
139 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Journal of translational medicine · 2024Pooled it
- Pooled it
- Biomarkers of therapeutic efficacy in adolescents and adults with 5q spinal muscular atrophy: a systematic review.Acta neurologica Belgica · 2023Pooled it
- Genetic factors for survival in amyotrophic lateral sclerosis: an integrated approach combining a systematic review, pairwise and network meta-analysis.BMC medicine · 2022Pooled it
- Prognostic models for amyotrophic lateral sclerosis: a systematic review.Journal of neurology · 2021Pooled it
- Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.JAMA neurology · 2026Trial
- Longitudinal course of neurofilament light chain levels in amyotrophic lateral sclerosis-insights from a completed randomized controlled trial with rasagiline.European journal of neurology · 2024Trial
- Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial.European journal of neurology · 2023Trial
- A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS.Annals of clinical and translational neurology · 2022Trial
- The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.Brain : a journal of neurology · 2021Trial
- Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.The New England journal of medicine · 2020Trial
- Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.Dialogues in clinical neuroscience · 2026Review
- Serum Neurofilament Light Chain and GFAP in Amyotrophic Lateral Sclerosis on a Commercial ECLIA Platform.Muscle & nerve · 2026Article
- Tofersen Treatment inMayo Clinic proceedings. Innovations, quality & outcomes · 2026Article
- From Vision to Validation: The Journey of Tofersen in Superoxide Dismutase 1 Gene-Associated Amyotrophic Lateral Sclerosis.Mayo Clinic proceedings. Innovations, quality & outcomes · 2026Article
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Beyond Biomarkers: Reclaiming the Central Role of Clinical Neurophysiology in Neuromuscular Disorders.Brain sciences · 2026Review
- Effects of Dietary Supplementation with Conjugated Linoleic Acid on Redox Marker Profiles and Neuroaxonal Degeneration in Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2026Article
- Analytical Performance and Evaluation in Clinical Cohorts of a Fully Automated Immunoassay for Plasma Glial Fibrillary Acidic Protein.Diagnostics (Basel, Switzerland) · 2026Article
- Integration of Serum Neurofilament Light Chain and Cortical Dysfunction Improves Diagnostic Accuracy in ALS.Annals of clinical and translational neurology · 2026Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Michael BenatarFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD. mbenatar@med.miami.edu jwuu@med.miami.edu.ORCID 0000-0003-4241-5135
Lanyu ZhangFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Lily WangFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Volkan GranitFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.ORCID 0000-0002-6519-7225
Jeffrey StatlandFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.ORCID 0000-0003-0790-5315
Richard BarohnFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Andrea SwensonFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
John RavitsFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Carlayne JacksonFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Ted M BurnsFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Jaya TrivediFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Erik P PioroFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.ORCID 0000-0002-0737-6065
James CaressFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.ORCID 0000-0002-5814-6083
Jonathan KatzFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Jacob L McCauleyFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.ORCID 0000-0002-1805-1733
Rosa RademakersFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Andrea MalaspinaFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Lyle W OstrowFrom Miller School of Medicine (M.B., L.Z., L.W., V.G., J.W.), University of Miami, FL; Kansas University Medical Center (J.S., R.B.), Kansas City; University of Iowa (A.S.), Iowa City; University of California San Diego (J.R.); University of Texas Health Science Center San Antonio (C.J.); University of Virginia (T.M.B.), Charlottesville; UT Southwestern Medical Center (J.T.), Dallas, TX; Cleveland Clinic (E.P.P.), OH; Wake Forest School of Medicine (J.C.), Winston-Salem, NC; California Pacific Medical Center (J.K.), San Francisco; John P Hussman Institute for Human Genomics (J.L.M.), Miami; Mayo Clinic Jacksonville (R.R.), FL; Blizard Institute (A.M.), Queen Mary University of London, UK; and Johns Hopkins University (L.W.O.), Baltimore, MD.
Joanne Wuu
CReATe Consortium
Funding
RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 TestingUL1TR002366 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mario Castro, JAMES STEVEN LEEDER · 2017 to 2026
$44.3MUncovering new genes and disease modifiers for ALS and related disordersU54NS092091 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Corey T McMillan · 2014 to 2026
$19.8MHeartland Institute for Clinical and Translational ResearchUL1TR000001 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI BAROHN, RICHARD J. · 2012 to 2015
$13.0MMulti-Center ALS Biomarker Validation Study (CReATe Biomarkers)U01NS107027 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BENATAR, MICHAEL, MALASPINA, ANDREA · 2018 to 2023
$3.5MNCATS NIH HHS UL1 TR000001NCATS NIH HHS UL1 TR002366NINDS NIH HHS U01 NS107027NINDS NIH HHS U54 NS092091
Abstract
objectiveTo identify preferred neurofilament assays and clinically validate serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) as prognostic and potential pharmacodynamic biomarkers relevant to amyotrophic lateral sclerosis (ALS) therapy development.
methodsIn this prospective, multicenter, longitudinal observational study of patients with ALS (n = 229), primary lateral sclerosis (n = 20), and progressive muscular atrophy (n = 11), biological specimens were collected, processed, and stored according to strict standard operating procedures (SOPs). Neurofilament assays were performed in a blinded manner by independent contract research organizations.
resultsFor serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e., technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples, respectively. Mean coefficients of variation for NfL in serum and CSF were both ∼3%. Mean coefficients of variation for pNfH in serum and CSF were ∼4%-5% and ∼2%-3%, respectively, in all assays. Baseline serum NfL concentration, but not pNfH, predicted the future Revised ALS Functional Rating Scale (ALSFRS-R) slope and survival. Incorporation of baseline serum NfL into mixed effects models of ALSFRS-R slopes yields an estimated sample size saving of ∼8%. Depending on the method used to estimate effect size, use of serum NfL (and perhaps pNfH) as pharmacodynamic biomarkers, instead of the ALSFRS-R slope, yields significantly larger sample size savings.
conclusionsSerum NfL may be considered a clinically validated prognostic biomarker for ALS. Serum NfL (and perhaps pNfH), quantified using the Simoa assay, has potential utility as a pharmacodynamic biomarker of treatment effect.
Indexed as
AdultAgedAmyotrophic Lateral SclerosisBiomarkersFemaleHumansIntermediate FilamentsMaleMiddle AgedPrognosisBiomarkers
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