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Microglia heterogeneity in vascular dementia pathology

Zhanfei Tan1, Dongchen Xu1, Yu Cao2

  • 1Wangjing Hospital, China Academy of Chinese Medical Science, Beijing 100102, China.

Iscience
|July 20, 2026
PubMed

Insights

Microglia show diverse activation states in vascular dementia (VaD). Understanding these distinct phenotypes is key to developing targeted therapies for this common dementia, moving beyond simplistic M1/M2 classifications.

Area of Science:

  • Neuroscience
  • Immunology
  • Neuropathology

Background:

  • Microglia display significant heterogeneity in phenotype and function across different brain conditions.
  • Vascular dementia (VaD), a common dementia, is characterized by cerebrovascular pathology that induces specific microglial activation states.

Purpose of the Study:

  • To review current knowledge of microglial phenotypes in neurological diseases, with a focus on their role in VaD.
  • To describe key VaD-associated microglial phenotypes and discuss their molecular drivers.

Main Methods:

  • Literature review synthesizing current understanding of microglial phenotypes in neurological disease.
  • Focus on microglial contributions to VaD following vascular insults like chronic cerebral hypoperfusion and stroke.
  • Description of specific microglial subsets, including ICAM and IPAM microglia, TREM1+-activated microglia, and cytokine-responsive microglia (CRM).

Main Results:

  • Identified spatially segregated microglial subsets (ICAM and IPAM) in ischemic territories.
  • Described TREM1+-activated microglia in hemorrhagic foci and cytokine-responsive microglia (CRM) in human VaD brains.
  • Discussed molecular drivers of microglial heterogeneity, challenging the M1/M2 dichotomy.

Conclusions:

  • Microglial heterogeneity in VaD is complex and region-specific, necessitating a move beyond the M1/M2 model.
  • Proposed a framework for developing precision immunomodulatory therapies for VaD.
  • Highlighted antibody-mediated approaches and in situ cellular reprogramming as potential future interventions for VaD.
Keywords:
Cell biologyMicrobiologyMolecular biology

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