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<p>The extent to which the cerebrovasculature is affected in various brain disorders is still not well understood. To address this, we established a transcriptomic repository of major vascular cell types and microglia to compare the global transcriptomic response in mouse models of three human brain disorders linked to neuroinflammation and associated vascular reactivity: Alzheimer’s disease (AD), traumatic brain injury (TBI), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Single-cell analysis of &gt;250,000 cells at different disease stages led to identification of two previously unknown vascular cell subtypes, expanded the endothelial zonation spectrum and allowed for a detailed analysis of the cellular and molecular responses. Surprisingly, most vascular cell types lacked major transcriptomic changes across the three conditions, while microglia exhibited significant, disease-specific transcriptional changes. Notably, microglial responses converged between late-stage TBI and AD, offering insights into the predisposition for neurodegeneration following TBI.</p>

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Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer’s, CADASIL, and Traumatic Brain Injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月16日

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  • K. D. Bjørnholm,
  • H. Li,
  • F. Del Gaudio,
  • G. Mocci,
  • W. Shao,
  • E. Baldisseri,
  • S. B. Rao,
  • C. Lindblad,
  • A. Fletcher-Sandersjöö,
  • E. Vázquez-Liébanas,
  • R. Pietilä,
  • L. Muhl,
  • R. Jiang,
  • C. Kalantzi,
  • J. Cheung,
  • S. Jin,
  • M. Svensson,
  • S. A. J. Lesnik Oberstein,
  • S. Syvänen,
  • M. A. Mäe,
  • R. Torp,
  • U. Lendahl,
  • H. Karlström,
  • E. P. Thelin,
  • P. Nilsson,
  • M. Vanlandewijck

摘要

The extent to which the cerebrovasculature is affected in various brain disorders is still not well understood. To address this, we established a transcriptomic repository of major vascular cell types and microglia to compare the global transcriptomic response in mouse models of three human brain disorders linked to neuroinflammation and associated vascular reactivity: Alzheimer’s disease (AD), traumatic brain injury (TBI), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Single-cell analysis of >250,000 cells at different disease stages led to identification of two previously unknown vascular cell subtypes, expanded the endothelial zonation spectrum and allowed for a detailed analysis of the cellular and molecular responses. Surprisingly, most vascular cell types lacked major transcriptomic changes across the three conditions, while microglia exhibited significant, disease-specific transcriptional changes. Notably, microglial responses converged between late-stage TBI and AD, offering insights into the predisposition for neurodegeneration following TBI.