Evidence map›Paper›PMID 41115958›Full record

ArticleNature medicine2026

Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis.

Ahmed Abdelhak, Gabriel Cerono, Fahime Sheikhzadeh, Adil Harroud, Kiarra Ning, Colin R Zamecnik, Gavin M Sowa, John Boscardin, Christian Cordano, Asritha Tubati and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Multiple sclerosis: 2026 update.Free neuropathology · 2026
    Review
  13. Review
  14. 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

24 authors.

Ahmed AbdelhakDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA. ahmed.abdelhak@ucsf.edu.ORCID http://orcid.org/0000-0001-9731-4169
Gabriel CeronoDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.
Fahime SheikhzadehIndependent researcher, San Francisco, CA, USA.
Adil HarroudThe Neuro (Montreal Neurological Institute-Hospital), Montréal, Quebec, Canada.
Kiarra NingDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0007-4433-4087
Colin R ZamecnikDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9477-1388
Gavin M SowaDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2089-8116
John BoscardinDepartments of Medicine and Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3121-9526
Christian CordanoDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1413-0442
Asritha TubatiDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.
Camille FouassierDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.
Eric D ChowDepartment of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8079-918X
Refujia GomezDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.
Adam SantanielloDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9816-5932
Kelsey C ZornDepartment of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1227-2137
Jill A HollenbachDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6572-7962
Jorge R OksenbergDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.
Bruce A C CreeDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7689-2533
Stephen L HauserDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4932-4001
Jonah R ChanDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2176-1242
Sergio E BaranziniDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0067-194X
Mitchell T WallinDepartment of Veterans Affairs, Multiple Sclerosis Center of Excellence, Washington, DC, USA.ORCID http://orcid.org/0000-0003-1061-5714
Michael R WilsonDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8705-5084
Ari J GreenDepartment of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA.

Funding

The Role of B cells in the Origin and Progression of Multiple SclerosisR35NS111644 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEPHEN L HAUSER · 2019 to 2026
$9.1M
NINDS NIH HHS R35 NS111644U.S. Department of Defense (United States Department of Defense) HT94252310499
6 · The paper itself

Abstract

The timing of the biological onset of multiple sclerosis (MS) is unclear. We used high-throughput discovery proteomics and samples from presymptomatic patients with MS and matched healthy controls to define the biological neurological onset and characterize the mechanisms involved. Remarkably, evidence of myelin injury was seen ~7 years before the symptomatic onset and preceded evidence of axonal injury by ~1 year. By contrast, astrocyte involvement became evident only at clinical onset. Numerous changes in the serum proteome indicate the involvement of interleukin 3 and nuclear factor kappa B pathways during the presymptomatic stage. Furthermore, people with MS with a previously reported distinct autoantibody signature showed increased immune cell activity compared to those without. We propose a protein biomarker panel that may help distinguish presymptomatic patients with MS from healthy controls, pending validation in future studies. Our findings can help understand the pathophysiology of MS as well as the cascade of central nervous system injury and might facilitate early detection of MS in high-risk people.

Indexed as

AxonsMultiple SclerosisMyelin SheathAdultAstrocytesAutoantibodiesBiomarkersCase-Control StudiesFemaleHumansMaleMiddle AgedNF-kappa BProteomicsAutoantibodiesBiomarkersNF-kappa B

Identifiers

PMID41115958
PMCPMC13052337

What OpenQuestion holds

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Registered trials

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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.