Evidence map›Paper›PMID 41416248›Full record

ArticleBrain communications2025

Stable isotope labelling kinetics of neurofilament light.

Claire A Leckey, Tatiana A Giovannucci, John B Coulton, Yingxin He, Chihiro Sato, Nupur Ghoshal, Tharini Vignarajah, Zane Jaunmuktane, Nicolas R Barthélemy, Henrik Zetterberg and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Claire A LeckeyUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.
Tatiana A GiovannucciUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.ORCID https://orcid.org/0000-0001-8978-6318
John B CoultonDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID https://orcid.org/0000-0002-1353-1180
Yingxin HeDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID https://orcid.org/0000-0003-2543-4553
Chihiro SatoDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Nupur GhoshalDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tharini VignarajahUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.
Zane JaunmuktaneUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.
Nicolas R BarthélemyDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Henrik ZetterbergUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.
Donald L ElbertDepartment of Neurology, University of Washington, Seattle, WA 98195, USA.
Kevin MillsUCL Great Ormond Street Institute of Child Health, Translational Mass Spectrometry Research Group, University College London, London WC1N 1EH, UK.
Selina WrayUCL Queen Square Institute of Neurology, Department of Neurodegenerative Disease, University College London, London WC1N 3BG, UK.ORCID https://orcid.org/0000-0003-3062-7050
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID https://orcid.org/0000-0002-7729-1702
Ross W PatersonUK Dementia Research Institute at University College London, London WC1N 6BT, UK.ORCID https://orcid.org/0000-0001-9372-3635

Funding

University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
NIA NIH HHS P30 AG066509
6 · The paper itself

Abstract

This study provides the first quantification of neurofilament light chain (NfL) kinetics in the human CNS using stable isotope labelling kinetics. NfL is elevated in CSF and blood across a range of traumatic, inflammatory and neurodegenerative diseases of the CNS, and has been increasingly included in clinical trials as a secondary or exploratory outcome measure of target engagement. Interpreting trajectories of NfL post-treatment has been challenging, prompting a greater need and focus on understanding its pathophysiology. We set out to measure NfL kinetics in the human CNS using stable isotope labelling kinetics. In human neurons derived from induced pluripotent stem cells, we show that NfL turnover is relatively slow, comparable to other long-lived proteins such as tau. We detected a delay of 3 to 6 days in the release of NfL into the media, unexpected for a passively released protein and supporting that controlled mechanisms of release could contribute to the appearance of NfL in the extracellular milieu. We optimized the kinetic NfL assay to measure the turnover of NfL in the human CNS. Participants with diagnosed primary tauopathies (

Indexed as

human CNSiPSC-derived neuronsneurodegenerationneurofilament light chainstable isotope labelling kinetics

Identifiers

PMID41416248
PMCPMC12709284

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.