Evidence mapPaperPMID 41735646Full record

ArticleNature aging2026

Identification of distinct and shared biomarker panels in different manifestations of cerebral small-vessel disease through proteomic profiling.

Ines Hristovska, Alexa Pichet Binette, Atul Kumar, Malin Wennström, Chris Gaiteri, Linda Karlsson, Olof Strandberg, Shorena Janelidze, Danielle van Westen, Erik Stomrud and 5 more

Abstract read
In one paragraph

Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Biological classification of memory clinic patients.Brain : a journal of neurology · 2026
    Article
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Ines HristovskaClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. ines.hristovska@med.lu.se.
Alexa Pichet BinetteClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Atul KumarClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-2166-4805
Malin WennströmCognitive Disorder Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Chris GaiteriDepartment of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
Linda KarlssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-0630-772X
Olof StrandbergClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0003-2869-8378
Danielle van WestenDiagnostic Radiology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-8649-9874
Erik StomrudClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Sebastian PalmqvistClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-9267-1930
Rik OssenkoppeleClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0003-1584-7477
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-8885-7724
Jacob W VogelDepartment of Clinical Sciences, Malmö, SciLifeLab, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-6394-9940
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.ORCID http://orcid.org/0000-0001-8467-7286

Funding

Alzheimer's Association SG-23-1061717Alzheimer's Association ZEN24-1069572Crafoordska Stiftelsen (Crafoord Foundation) 20230790EU Joint Programme - Neurodegenerative Disease Research (Programi i Përbashkët i BE-së për Kërkimet mbi Sëmundjet Neuro-degjeneruese) 2019-03401Hjärnfonden (Swedish Brain Foundation) FO2021-0293Hjärnfonden (Swedish Brain Foundation) FO2023-0163Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (King Gustaf V and Queen Victoria's Foundation of Freemasons) 2020-O000028Vetenskapsrådet (Swedish Research Council) 2018-02052Vetenskapsrådet (Swedish Research Council) 2021-02219Vetenskapsrådet (Swedish Research Council) 2022-00775
6 · The paper itself

Abstract

The pathophysiology underlying various manifestations of cerebral small-vessel disease (cSVD) remains poorly understood. Using high-throughput proteomics, we identified common and distinct proteomic signatures of white matter lesions (WMLs), microbleeds, infarcts and their subtypes, measured in 1,670 living patients. Across all cSVD manifestations, markers of extracellular matrix dysregulation and vascular remodeling were increased, including ELN, POSTN, CCN2 and especially MMP12, implicating endothelial and smooth muscle cells of the brain. These proteins were validated in cerebrospinal fluid from two additional datasets, and a subset detected in plasma predicted future cerebrovascular events in the UK Biobank better than risk scores currently used in clinical practice. Analysis focusing on WMLs found microglial-associated proteins associated with faster WML progression, whereas specific neuron-derived proteins mediated the link between WMLs and longitudinal cognitive decline. These data provide a comprehensive atlas of cSVD biomarkers, and our findings provide a promising roadmap for future diagnostics and therapeutics.

Indexed as

Cerebral Small Vessel DiseasesProteomicsBiomarkersBrainFemaleHumansMaleMiddle AgedPeriostinWhite MatterBiomarkersPeriostin

Identifiers

PMID41735646
PMCPMC13004690

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.