Higher Education Press
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.
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