image: This study illustrates the spatiotemporal dynamics of neuron subtype changes within the entorhinal cortex–hippocampal circuit during Alzheimer’s disease progression. EC-stellate neurons progressively decline, while GFAP⁺ neurons emerge and expand from CA3 to CA1 and entorhinal cortex, indicating identity reprogramming and involvement in AD pathology.
Credit: Yuting Ma, Juan Zhang, Hankui Liu, Dingfeng Li, Sicheng Guo, Jialuo Han, Lei Wang, Shaojun Yu, Xi Su, Yongchang Gao, Xiumei Lin, A San, Yushan Peng, Guibo Li, Hui Jiang, Wei Wang, Huanming Yang, Jian Wang, Shida Zhu, Lijian Zhao, Jianguo Zhang, Qiang Liu
This study constructs a spatiotemporal single-nucleus transcriptomic atlas of neurons in the entorhinal cortex–hippocampal (EC-HPC) circuit during Alzheimer’s disease (AD) progression. By performing Smart-seq2-based single-nucleus RNA sequencing on neurons from APP/PS1 transgenic mice and wild-type controls across different brain regions and disease stages, the study reveals two distinct neuronal populations associated with AD pathology: progressively lost EC-stellate neurons and expanding GFAP⁺ neurons with glia-like features. These findings highlight neuronal identity changes and energy metabolism dysfunction in AD, offering new insights into early diagnosis and intervention.
Journal
Protein & Cell
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
Spatiotemporal characterization of disease-associated neurons in the entorhinal cortex-hippocampal circuit during Alzheimer’s disease progression
Article Publication Date
10-Jun-2025