Article
作者: Wang, Pan ; Jin, Bufan ; Wang, Jian ; Pan, Catherine ; Lei, Junjie ; Cheng, Mengnan ; Tian, Chen ; Wang, Shengpeng ; Liu, Longqi ; Chen, Jing ; Su, Xinhui ; Xu, Xun ; Zhang, Jing ; He, Youzhe ; Luo, Ting ; Yang, Tao ; Luo, Benyan ; Sun, Bing ; Zhu, Keqing ; Wu, Juanli ; Fan, Zhongqin ; Yang, Ying ; Li, Xiao-Ming ; Tang, Yuanchun ; Shen, Yi ; Bao, Aimin ; Gao, Yue ; Duan, Shumin ; Jiang, Peiran ; Liu, Yuyang ; Han, Lei ; Xu, Bin ; Wei, Yanrong ; Xu, Zhi ; Liu, Shiping ; Tao, Quyuan ; Zheng, Huiwen ; Jiang, Yujia ; Wen, Huiying ; Yao, Jianhua ; Zhuang, Zhenkun ; Wang, Lifang ; Peng, Guoping ; Fang, Zheng ; Wu, Zihan ; Guo, Zhen ; Yu, Jiayi
We employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate the gene expression and cell composition changes in human hippocampus with or without Alzheimer's disease (AD). The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatial specificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD, with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) a globally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largely unaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloid-beta (Aβ) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques. Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelin protein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.