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Cited by 293Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials

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Miao, Jifei, Ma, Haixia, Yang, Yang, Liao, Yuanpin, Lin, Cui, Zheng, Juanxia, Yu, Muli, Lan, Jiao·2023·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2023.1201982PMC PMC10309009
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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed the critical role of microglia in AD pathogenesis. This review provides a comprehensive summary of the current understanding of microglial involvement in AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact on synaptic plasticity and neuronal regulation. Furthermore, recent developments in drug discovery targeting microglia in AD are reviewed, highlighting potential avenues for therapeutic intervention. This review emphasizes the essential role of microglia in AD and provides insights into potential treatments.

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  • The older binary language of resting versus activated microglia is too limited.

    “This older binary language is now considered too limited.”

    From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [11]

    Section 3 (Microglia activation; page unavailable) says the M1/M2 binary classification is contested and that intermediate phenotypes better reflect microglial activation states. This supports the broader point that binary language is too limited, but the paper does not specifically make that criticism of the resting-versus-activated distinction. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Phagocytosis is the major mechanism for Aβ aggregate clearance in the brain, with microglia as the main effector cells for engulfing and degrading Aβ.

    “Phagocytosis is the major mechanism contributing to Aβ aggregate clearance in the brain, with microglia serving as the main effector cells for engulfing and degrading Aβ (30).”

    From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [30]

    Section 4 says microglial phagocytosis is essential for clearing Aβ deposits and describes microglia engulfing Aβ. Section 4.4 also describes other clearance routes and cells, but does not establish that phagocytosis is the major clearance mechanism or that microglia are the main effector cells. Page numbers were not available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In disease, microglial capacities can become either protective or damaging depending on context, timing, and molecular state.

    “in disease, these same capacities can become either protective or damaging depending on context, timing, and molecular state [10,11,12].”

    From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [11]

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Authors
Miao, J., Ma, H., Yang, Y., Liao, Y., Lin, C., Zheng, J., Yu, M., & Lan, J.
Affiliations
  • Peking University (CN)
  • Guangzhou University of Chinese Medicine (CN)
Corresponding author
Lan, Jiao
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2023-06-15
Volume
15
Pages
1201982-1201982
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2023.1201982
PMC
PMC10309009
OpenAlex
W4380680803
Cited by
293
References
452
Citations by year
2026: 99 · 2025: 128 · 2024: 59 · 2023: 7
FWCI
7.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, microglia, neuroinflammation, microglial phenotype, phagocytosis, synaptic plasticity, protein aggregation, genetic factors, neurodegeneration

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