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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月24日

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  • Ines Hristovska,
  • Alexa Pichet Binette,
  • Atul Kumar,
  • Malin Wennström,
  • Chris Gaiteri,
  • Linda Karlsson,
  • Olof Strandberg,
  • Shorena Janelidze,
  • Danielle van Westen,
  • Erik Stomrud,
  • Sebastian Palmqvist,
  • Rik Ossenkoppele,
  • Niklas Mattsson-Carlgren,
  • Jacob W. Vogel,
  • Oskar Hansson

摘要

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.