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Updated: May 22, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Targeting microglia: A new strategy for the treatment of Alzheimer's disease
Manyv Zheng1, Mingjuan Yang1, Wenya Su1
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
Abstract:
Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, and chronic neuroinflammation, remains without curative therapies. Emerging evidence underscores microglia, the brain's resident immune cells, as pivotal players in AD pathogenesis, exerting dual roles in neuroprotection and neurotoxicity. This review synthesizes current knowledge on microglial dynamics, including their heterogeneous activation states (e.g., disease-associated microglia), metabolic reprogramming, aging-related dysfunction, and subset heterogeneity, which collectively influence Aβ clearance, tau propagation, and synaptic integrity. We highlight the interplay between microglial receptors-such as TREM2, APOE, and neurotransmitter receptors (e.g., cholinergic, glutamatergic, and cannabinoid receptors)-and AD pathology, emphasizing their roles in modulating neuroinflammation, phagocytosis, and neuronal excitotoxicity. Furthermore, we evaluate therapeutic strategies targeting microglia, including pharmacologic modulation of neuroinflammatory pathways, metabolic interventions, and cell transplantation, which aim to restore homeostatic microglial functions. Challenges in clinical translation, such as temporal specificity of interventions and microglial plasticity, are critically discussed. By integrating recent advances in single-cell genomics and neuroimmunology, this review provides a roadmap for developing microglia-centric therapies to disrupt the vicious cycle of neuroinflammation and neurodegeneration in AD, offering novel insights for future research and therapeutic innovation.
Insights
Microglia, the brain's immune cells, play a key role in Alzheimer's disease (AD) progression. Targeting microglial dysfunction offers a promising therapeutic avenue for AD neuroinflammation and neurodegeneration.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
- Cellular Biology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no cure, marked by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation.
- Microglia, the central nervous system's immune cells, are increasingly recognized as critical players in AD pathogenesis, exhibiting both protective and detrimental functions.
Purpose of the Study:
- To synthesize current knowledge on microglial dynamics in Alzheimer's disease.
- To explore the role of microglial receptors and their interplay with AD pathology.
- To evaluate therapeutic strategies targeting microglia for AD treatment.
Main Methods:
- Review of current literature on microglial biology and Alzheimer's disease.
- Analysis of microglial activation states, metabolic reprogramming, and aging-related dysfunction.
- Examination of the roles of specific microglial receptors (TREM2, APOE) and neurotransmitter receptors.
Main Results:
- Microglial heterogeneity, including disease-associated microglia and aging-related dysfunction, significantly impacts Aβ clearance, tau propagation, and synaptic integrity.
- Interactions between microglial receptors and AD pathology modulate neuroinflammation, phagocytosis, and neuronal excitotoxicity.
- Various therapeutic strategies targeting microglial pathways show potential for restoring homeostatic functions.
Conclusions:
- Microglia are central to AD pathogenesis, with their diverse states influencing disease progression.
- Targeting microglial receptors and metabolic pathways offers a promising strategy for AD therapeutics.
- Developing effective microglia-centric therapies requires addressing challenges like temporal specificity and microglial plasticity.
