Evidence map›Paper›PMID 39673059›Full record

ArticleJournal of neuroinflammation2024

Tyro3 and Gas6 are associated with white matter and myelin integrity in multiple sclerosis.

Igal Rosenstein, Lenka Novakova, Hlin Kvartsberg, Anna Nordin, Sofia Rasch, Elzbieta Rembeza, Sofia Sandgren, Clas Malmeström, Stefanie Fruhwürth, Markus Axelsson and 3 more

Abstract read
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In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

13 authors.

Igal Rosenstein *Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden. igal.rosenstein@vgregion.se.ORCID http://orcid.org/0000-0002-5078-9690
Lenka Novakova *Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Hlin KvartsbergClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Anna NordinDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Sofia RaschClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Elzbieta RembezaClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Sofia SandgrenDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Clas MalmeströmDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Stefanie FruhwürthDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Markus AxelssonDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Kaj BlennowClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Henrik ZetterbergClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Jan LyckeDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.

Funding

AD Strategic Fund and the Alzheimer's Association ADSF-21-831376-CAlzheimer Drug Discovery Foundation (ADDF), USA 201809-2016862Alzheimer's Association 2021 Zenith Award ZEN-21-848495Alzheimer's Association 2022-2025 Grant SG-23-1038904 QCD Strategic Fund and the Alzheimer's Association ADSF-21-831381-CEuropean Union Joint Program for Neurodegenerative Disorders JPND2019-466-236European Union's Horizon Europe research and innovation programme 101053962Hjärnfonden FO2017-0243Hjärnfonden, Sweden FO2022-0270National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL UKDRI-1003Swedish Alzheimer Foundation AF-930351Swedish State Support for Clinical Research ALFGBG-715986Swedish State Support for Clinical Research ALFGBG-722081Swedish State Support for Clinical Research ALFGBG-984087), the European Union Joint Programme - Neurodegenerative Disease Research JPND2021-00694Vetenskapsrådet 2017-00915Vetenskapsrådet 2023-00356
6 · The paper itself

Abstract

backgroundThe Gas6/TAM (Tyro3, Axl, and Mer) receptor system has been implicated in demyelination and delayed remyelination in experimental animal models, but data in humans are scarce. We aimed to investigate the role of Gas6/TAM in neurodegenerative processes in multiple sclerosis (MS).

methodsFrom a prospective 5-year follow-up study, soluble Gas6/TAM biomarkers were analyzed in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay (ELISA) at baseline in patients with relapsing-remitting MS (RRMS) (n = 40), progressive MS (PMS) (n = 20), and healthy controls (HC) (n = 25). Brain volumes, including myelin content (MyC) and white matter (WM) were measured by synthetic magnetic resonance imaging at baseline, 12 months, and 60-month follow-up. Associations with brain volume changes were investigated in multivariable linear regression models. Gas6/TAM concentrations were also determined at 12 months follow-up in RRMS to assess treatment response.

resultsBaseline concentrations of Tyro3, Axl, and Gas6 were significantly higher in PMS vs. RRMS and HC. Mer was higher in PMS vs. HC. Tyro3 and Gas6 were associated with reduced WM (β = 25.5, 95% confidence interval [CI] [6.11-44.96, p = 0.012; β = 11.4, 95% CI [0.42-22.4], p = 0.042, respectively) and MyC (β = 7.95, 95%CI [1.84-14.07], p = 0.012; β = 4.4, 95%CI [1.04-7.75], p = 0.012 respectively) at 60 months. Patients with evidence of remyelination at last follow-up had lower baseline soluble Tyro3 (p = 0.033) and Gas6 (p = 0.014). Except Mer, Gas6/TAM concentrations did not change with treatment in RRMS. DISCUSSION: Our data indicate a potential role for the Gas6/TAM receptor system in neurodegenerative processes influencing demyelination and ineffective remyelination.

Indexed as

Intercellular Signaling Peptides and ProteinsMyelin SheathReceptor Protein-Tyrosine KinasesWhite MatterAdultAxl Receptor Tyrosine KinaseBiomarkersFemaleFollow-Up StudiesGrowth Arrest-Specific Protein 6HumansMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisProto-Oncogene ProteinsAxl Receptor Tyrosine KinaseBiomarkersGrowth Arrest-Specific Protein 6Intercellular Signaling Peptides and ProteinsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesTYRO3 protein, humanBiomarkersDemyelinationInnate immunityQuantitative MRIRemyelination

Identifiers

PMID39673059
PMCPMC11645787

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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.