Jia Yangjie, Wang Xia, Chen Yanyu, Qiu Wenying, Ge Wei, Ma Chao
Department of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 5 Dongdansantiao, Dongcheng District, Beijing, 100005, China.
State Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 5 Dongdansantiao, Dongcheng District, Beijing, 100005, China.
Mol Neurobiol. 2021 Aug;58(8):4007-4027. doi: 10.1007/s12035-021-02356-3. Epub 2021 Apr 27.
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.
阿尔茨海默病（AD）是最常见的神经退行性疾病。AD最早的神经病理学变化出现在内嗅皮质（EC）区域。针对内嗅皮质退变的治疗策略和预防措施在AD早期具有重要价值。在本研究中，对AD的EC样本和非AD对照EC样本进行了基于Illumina RNA测序的转录组分析以及基于TMT标记的蛋白质组分析，以对RNA和蛋白质进行谱分析。采用免疫组织化学法验证蛋白质表达。综合分析后，在转录组和蛋白质组数据中均检测到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），AD与对照相比有6个基因呈相反趋势。在这51个基因中挑选出前6个基因（GABRG2、CACNG3、CACNB4、GABRB2、GRIK2和SLC17A6），它们与“离子转运”相关。相关性分析表明蛋白质表达水平与神经病理学变化呈负相关。总之，转录组和蛋白质组的综合分析为AD中跨脑区离子转运失调提供了证据，这可能是引发病理变化的关键信号通路。本研究可能为AD患者EC中最早出现的变化提供新的见解，并为AD的预防和治疗提供新的靶点。
