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Cited by 18Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity

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Wang, Na, Cai, Lujian, Pei, Xinyu, Lin, Zhihao, Huang, Lihong, Liang, Chensi, Wei, Min, Shao, Lin +14 more·2024·iScience
DOI 10.1016/j.isci.2024.110006PMC PMC11167441
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Abstract

Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

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Authors
Wang, N., Cai, L., Pei, X., Lin, Z., Huang, L., Liang, C., Wei, M., Shao, L., Guo, T., Huang, F., Luo, H., Zheng, H., Chen, X.-F., Leng, L., Zhang, Y.-W., Wang, X., Zhang, J., Guo, K., Wang, Z., Zhang, H., Zhao, Y., & Xu, H.
Affiliations
  • Xiamen University (CN)
  • Chongqing Medical University (CN)
Corresponding author
  • Wang, Zhanxiang
  • Zhang, Hongsheng
  • Zhao, Yingjun
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2024-06
Volume
27
Issue
6
Pages
110006
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2024.110006
PMC
PMC11167441
OpenAlex
W4396980195
Cited by
18
References
25
Citations by year
2026: 12 · 2025: 6
FWCI
4.66
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Natural Science Foundation of Chongqing Municipality (CSTB2022NSCQ-LZX0033)
  • National Key Research and Development Program of China (2021ZD0202402, 2021YFA1101401)
  • University of Science and Technology of China
  • National Natural Science Foundation of China (82071213, 82271472, 92049202, 92149303)
  • Chongqing Municipal Education Commission (KJQN202200479)
  • Sichuan University
  • Xiamen University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
apolipoprotein E, microglia, astrocytes, neuronal senescence, synaptotoxicity, GPNMB, APOE ε4, APOE3, neurite outgrowth, Alzheimer's disease, extracellular vesicles

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