Alzheimer's disease (AD) is a progressive neurodegenerative disorder that mostly strikes the elderly. However, the exact molecular and cellular pathogenesis of AD, especially the dynamic changes of neurons during disease progression, remains poorly understood. Here we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional changes of hippocampal neurons in APP23 mouse model of AD. We performed snRNA-seq using a modified Smart-seq2 technique on 3,280 neuronal nuclei from the hippocampus of young and aged APP23 and control mice and identified four distinct subpopulations. Comparative transcriptional analysis showed multiple changes in different subtypes of hippocampal neurons of APP23 mice in comparison to control mice, as well as the transcriptional changes in these neurons during disease progression. Our findings revealed multiple neuronal subtype-specific transcriptional changes that may lead to targets for future studies of AD.

中文翻译：

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单核RNA测序揭示了阿尔茨海默氏病APP23小鼠模型中海马神经元的转录变化。

阿尔茨海默氏病（AD）是一种进行性神经退行性疾病，主要侵袭老年人。但是，AD的确切分子和细胞发病机制，尤其是疾病进展过程中神经元的动态变化，仍然知之甚少。在这里，我们使用单核RNA测序（snRNA-seq）来访问AD APP23小鼠模型中海马神经元的转录变化。我们使用改良的Smart-seq2技术对来自年轻和老年APP23和对照小鼠海马的3,280个神经元核进行了snRNA-seq，并鉴定了四个不同的亚群。比较转录分析显示，与对照组小鼠相比，APP23小鼠海马神经元不同亚型的多重变化，以及疾病进展过程中这些神经元的转录变化。