Proteomic and Transcriptomic Analyses Reveal Pathological Changes in the Entorhinal Cortex Region that Correlate Well with Dysregulation of Ion Transport in Patients with Alzheimer's Disease
Proteomic and Transcriptomic Analyses Reveal Pathological Changes in the Entorhinal Cortex Region that Correlate Well with Dysregulation of Ion Transport in Patients with Alzheimer's Disease
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蛋白质组学和转录组学分析揭示内嗅皮层区域的病理变化与阿尔茨海默病患者的离子转运失调密切相关
DOI：
10.1007/s12035-021-02356-3
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发表时间：
2021-04-27
影响因子：
5.1
通讯作者：
Ma, Chao
中科院分区：
文献类型：
--
作者：
Jia, Yangjie;Wang, Xia;Ma, Chao
阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病。AD最早的神经病理学改变出现在内嗅皮层（EC）区域。治疗策略和预防措施，以防止内嗅变性将是非常有价值的早期阶段的AD。在本研究中，对AD EC样品和非AD对照EC样品进行基于Illumina RNA-seq的转录组和基于TMT标记的蛋白质组的RNA和蛋白质谱分析。免疫组织化学用于验证蛋白质表达。综合分析后，在转录组和蛋白质组数据中检测到57个基因，其中51个基因的变化趋势相似（7个上调，44个下调），6个基因的变化趋势相反。在51个基因中选择前6个基因（GABRG 2、CACNG 3、CACNB 4、GABRB 2、GRIK 2和SLC 17 A6），并且与“离子转运”相关。相关分析显示，蛋白表达水平与神经病理改变呈负相关。总之，整合转录组和蛋白质组分析提供了证据，在AD的跨脑区域的离子转运失调，这可能是一个关键的信号通路，启动病理。本研究可能为AD的早期EC变化提供新的见解，并为AD的预防和治疗提供新的靶点。
Alzheimer's disease (AD) is the most common neurodegenerative disorder. The earliest neuropathology of AD appears in entorhinal cortex (EC) regions. Therapeutic strategies and preventive measures to protect against entorhinal degeneration would be of substantial value in the early stages of AD. In this study, transcriptome based on the Illumina RNA-seq and proteome based on TMT-labelling were performed for RNA and protein profiling on AD EC samples and non-AD control EC samples. Immunohistochemistry was used to validate proteins expressions. After integrated analysis, 57 genes were detected both in transcriptome and proteome data, including 51 in similar altering trends (7 upregulated, 44 downregulated) and 6 in inverse trends when compared AD vs. control. The top 6 genes (GABRG2, CACNG3, CACNB4, GABRB2, GRIK2, and SLC17A6) within the 51 genes were selected and related to "ion transport". Correlation analysis demonstrated negative relationship of protein expression level with the neuropathologic changes. In conclusion, the integrate transcriptome and proteome analysis provided evidence for dysregulation of ion transport across brain regions in AD, which might be a critical signaling pathway that initiates pathology. This study might provide new insight into the earliest changes occurring in the EC of AD and novel targets for AD prevention and treatment.