The decreased astrocyte-microglia interaction reflects the early characteristics of Alzheimer’s disease
Kefu Liu,
Ailikemu Aierken,
Mengyao Liu,
Nazakat Parhat,
Wei Kong,
Xingyu Yin,
Gang Liu,
Ding Yu,
Jie Hong,
Junjun Ni,
Zhenzhen Quan,
Xiaoyun Liu,
Simei Ji,
Jian Mao,
Weijun Peng,
Chao Chen,
Yan Yan,
Hong Qing
Affiliations
Kefu Liu
MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410083, Hunan, China; Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Ailikemu Aierken
MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410083, Hunan, China; Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Mengyao Liu
Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
Nazakat Parhat
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Wei Kong
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Xingyu Yin
MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410083, Hunan, China
Gang Liu
Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
Ding Yu
Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
Jie Hong
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Junjun Ni
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Zhenzhen Quan
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Xiaoyun Liu
Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
Simei Ji
Department of Biology, Shenzhen MSU-BIT University, Shenzhen 518172, China
Jian Mao
Zhengzhou Tobacco Research Institute of China National Tobacco Company, Zhengzhou 450001, China
Weijun Peng
Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; National Clinical Research Center for Metabolic Diseases, Changsha, Hunan 410011, China
Chao Chen
MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410083, Hunan, China
Yan Yan
Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China; Corresponding author
Hong Qing
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Department of Biology, Shenzhen MSU-BIT University, Shenzhen 518172, China; Corresponding author
Summary: Alzheimer’s disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aβ is a typical AD hall marker, but Aβ-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aβ-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aβ-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.
