Cited by 104Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances

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Deng, Qianting, Wu, Chongyun, Parker, Emily, Liu, Timon Cheng-Yi, Duan, Rui, Yang, Luodan·2023·Aging and disease

DOI 10.14336/ad.2023.0907PMC PMC11272214

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Abstract

Alzheimer's disease, one of the most common forms of dementia, is characterized by a slow progression of cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered by various side effects and limited efficacy. Despite considerable research, practical treatments for AD have not been developed. Increasing evidence shows that glial cells, especially microglia and astrocytes, are essential in the initiation and progression of AD. During AD progression, activated resident microglia increases the ability of resting astrocytes to transform into reactive astrocytes, promoting neurodegeneration. Extensive clinical and molecular studies show the involvement of microglia and astrocyte-mediated neuroinflammation in AD pathology, indicating that microglia and astrocytes may be potential therapeutic targets for AD. This review will summarize the significant and recent advances of microglia and astrocytes in the pathogenesis of AD in three parts. First, we will review the typical pathological changes of AD and discuss microglia and astrocytes in terms of function and phenotypic changes. Second, we will describe microglia and astrocytes' physiological and pathological role in AD. These roles include the inflammatory response, "eat me" and "don't eat me" signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, and demyelination. Last, we will review the pharmacological and non-pharmacological therapies targeting microglia and astrocytes in AD. We conclude that microglia and astrocytes are essential in the initiation and development of AD. Therefore, understanding the new role of microglia and astrocytes in AD progression is critical for future AD studies and clinical trials. Moreover, pharmacological, and non-pharmacological therapies targeting microglia and astrocytes, with specific studies investigating microglia and astrocyte-mediated neuronal damage and repair, may be a promising research direction for future studies regarding AD treatment and prevention.

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The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer’s Disease
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Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
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Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline
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Astrocytes: Role and Functions in Brain Pathologies
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Pathophysiology of the Neurovascular Unit: Disease Cause or Consequence?
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Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease
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Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia
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Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
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Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting
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TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
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The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease
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Microglia contributes to plaque growth by cell death due to uptake of amyloid β in the brain of Alzheimer's disease mouse model: Aβ Plaque Formation and Microglial Activation
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Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology
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Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease
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Statins Promote the Degradation of Extracellular Amyloid β-Peptide by Microglia via Stimulation of Exosome-associated Insulin-degrading Enzyme (IDE) Secretion
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TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy
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Activated microglia mitigate Aβ-associated tau seeding and spreading
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Microglia contribute to the propagation of Aβ into unaffected brain tissue
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Microglia in Brain Development, Homeostasis, and Neurodegeneration
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Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions
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Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease
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Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease: A Randomized Clinical Trial
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TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination
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Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes
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Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting
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Authors: Deng, Q., Wu, C., Parker, E., Liu, T. C.-Y., Duan, R., & Yang, L.
Affiliations: South China Normal University (CN)
Augusta University (US)
Corresponding author: Duan, Rui
Yang, Luodan
ORCID: Liu, Timon Cheng-Yi
Duan, Rui
Yang, Luodan
Venue: Aging and disease
Publisher: Aging and Disease
Published: 2023
Volume: 15
Issue: 4
Pages: 0
ISSN: 2152-5250 (ISSN-L)
DOI: 10.14336/ad.2023.0907
PMC: PMC11272214
OpenAlex: W4387196264
Cited by: 102
References: 302
Citations by year: 2026: 38 · 2025: 43 · 2024: 21
FWCI: 2.66
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Aging and Disease (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (32100918, 31971096, 31771256)
China Postdoctoral Science Foundation (2022 T150227, SL2022B04J00013)
National Key Research and Development Program of China (2017YFB0403801)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, microglia, astrocytes, neuroinflammation, reactive astrocytes, microglial activation, amyloid-beta, synaptic pruning, synaptic loss, remyelination, demyelination, neurodegeneration, therapeutic target
MeSH terms: Alzheimer Disease, Animals, Astrocytes, Humans, Microglia

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Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances

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