Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity
Year: 2024
Type: article
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.
Source: iScience
Authors: 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
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: National Natural Science Foundation of China, Chongqing Medical University, Sichuan University, Natural Science Foundation of Chongqing, Chongqing Municipal Education Commission, Xiamen University, University of Science and Technology of China, Centre Scientifique et Technique du Bâtiment, National Key Research and Development Program of China
OpenAlex ID: W4396980195