Microglia heterogeneity in vascular dementia pathology

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

iScienceLast synced 7/21/2026Status: syncedPMID: 42473665 pmidDOI: 10.1016/j.isci.2026.116222

Summary Microglia exhibit remarkable phenotypic heterogeneity and functional plasticity across brain regions, time, and disease states. In vascular dementia (VaD)—the second most common dementia—cerebrovascular pathology drives distinct microglial activation states. This review synthesizes current understanding of microglial phenotypes in neurological disease, focusing on their contributions to VaD following vascular insults such as chronic cerebral hypoperfusion and stroke. Key VaD-associated phenotypes are described, including spatially segregated subsets in ischemic territories (ICAM and IPAM microglia),-activated microglia in hemorrhagic foci, and cytokine-responsive microglia (CRM) identified in human VaD brain. The molecular drivers of this heterogeneity are discussed, arguing for moving beyond the reductive M1/M2 dichotomy. The broader significance lies in a proposed framework for microglia-targeted therapeutic strategies, encompassing precision immunomodulation, antibody-mediated approaches, andcellular reprogramming as promising avenues for future intervention. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Molecular biology; Microbiology; Cell biology teaser abs0020

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