iScience (Jun 2024)
Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity
- Na Wang,
- Lujian Cai,
- Xinyu Pei,
- Zhihao Lin,
- Lihong Huang,
- Chensi Liang,
- Min Wei,
- Lin Shao,
- Tiantian Guo,
- Fang Huang,
- Hong Luo,
- Honghua Zheng,
- Xiao-fen Chen,
- Lige Leng,
- Yun-wu Zhang,
- Xin Wang,
- Jie Zhang,
- Kai Guo,
- Zhanxiang Wang,
- Hongsheng Zhang,
- Yingjun Zhao,
- Huaxi Xu
Affiliations
- Na Wang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Lujian Cai
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Xinyu Pei
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Zhihao Lin
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Lihong Huang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, China
- Chensi Liang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Min Wei
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Lin Shao
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Tiantian Guo
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Fang Huang
- Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing 400016, China
- Hong Luo
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Honghua Zheng
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Xiao-fen Chen
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Lige Leng
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Yun-wu Zhang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Xin Wang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, China
- Jie Zhang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China
- Kai Guo
- Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing 400016, China
- Zhanxiang Wang
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; Corresponding author
- Hongsheng Zhang
- Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), Chongqing 400016, China; Corresponding author
- Yingjun Zhao
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; Corresponding author
- Huaxi Xu
- Center for Brain Sciences, First Affiliated Hospital of Xiamen University, Institute of Neuroscience, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, Fujian 361005, China; Institute for Brain Science and Disease, Chongqing Medical University, Chongqing 400016, China
- Journal volume & issue
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Vol. 27,
no. 6
p. 110006
Abstract
Summary: 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.
