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<p>Alzheimer’s disease (AD) is a widespread neurodegenerative condition with cognitive and behavioral decline. Astrocytes and microglia, the primary glial cells in the central nervous system, are deeply involved in AD development. Their functional impairments, such as astrocytic shifts in phenotype, blood-brain barrier breakdown, and glymphatic failure, along with microglial “dual phagocytic dysfunction”, including impaired amyloid-beta (Aβ) clearance and overactive phagocytosis of healthy synapses, imbalanced inflammation, and metabolic abnormalities, are key drivers of disease progression. Growing research indicates that physical activity, as a non-drug intervention, exerts significant regulatory effects on glial cell function. Exercise regulates the polarization of both astrocytes and microglia, enhances their phagocytic abilities, improves mitochondrial metabolism, and alleviates neuroinflammatory responses. This review outlines the normal physiological roles of astrocytes and microglia, details their pathological alterations in AD, and explores how exercise targets these glial cells to alleviate AD pathology, offering valuable perspectives for potential therapeutic approaches.</p>

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Role Shift of Glial Cells from Physiology to Pathology in Alzheimer’s Disease: The Regulatory Impact of Exercise

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Runze Liu,
  • Qianting Deng,
  • Li Gong,
  • Luodan Yang

摘要

Alzheimer’s disease (AD) is a widespread neurodegenerative condition with cognitive and behavioral decline. Astrocytes and microglia, the primary glial cells in the central nervous system, are deeply involved in AD development. Their functional impairments, such as astrocytic shifts in phenotype, blood-brain barrier breakdown, and glymphatic failure, along with microglial “dual phagocytic dysfunction”, including impaired amyloid-beta (Aβ) clearance and overactive phagocytosis of healthy synapses, imbalanced inflammation, and metabolic abnormalities, are key drivers of disease progression. Growing research indicates that physical activity, as a non-drug intervention, exerts significant regulatory effects on glial cell function. Exercise regulates the polarization of both astrocytes and microglia, enhances their phagocytic abilities, improves mitochondrial metabolism, and alleviates neuroinflammatory responses. This review outlines the normal physiological roles of astrocytes and microglia, details their pathological alterations in AD, and explores how exercise targets these glial cells to alleviate AD pathology, offering valuable perspectives for potential therapeutic approaches.