Jian Chongdong, Wei Lei, Mo Ruikang, Li Rongjie, Liang Lucong, Chen Liechun, Zou Chun, Meng Youshi, Liu Ying, Zou Donghua
Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Aging Neurosci. 2021 Sep 20;13:731180. doi: 10.3389/fnagi.2021.731180. eCollection 2021.
Alzheimer's disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.
阿尔茨海默病（AD）是一种常见的神经退行性疾病。其发病隐匿，进展缓慢，诊断困难。此外，其潜在的分子和细胞机制仍不清楚。在本研究中，对48例AD患者前额叶皮质的单细胞RNA测序（scRNA-seq）数据进行了聚类分析。每个样本模块被鉴定为一种特定的AD细胞类型，确定了八种主要脑细胞类型，并通过拟时间分析进一步探索了每种细胞类型的功能失调演变。然后使用相关性分析来探索AD细胞类型与病理特征之间的关系。特别是，通过细胞通讯分析研究了AD患者神经元与胶质细胞之间的细胞间通讯。在患者中，神经元细胞和胶质细胞与病理特征显著相关，胶质细胞似乎通过配体-受体轴通讯在AD的发展中起关键作用。使用五种建模方法确定了参与这两种细胞类型通讯的标记基因：逻辑回归、多元逻辑回归、最小绝对收缩和选择算子（LASSO）以及支持向量机（SVM）。LASSO建模确定CXCR4、EGFR、MAP4K4和IGF1R是这种通讯中的关键基因。我们的结果支持小胶质细胞通过配体-受体轴通讯在AD的发生和发展中起作用的观点。特别是，我们的分析确定CXCR4、EGFR、MAP4K4和IGF1R是AD潜在的生物标志物和治疗靶点。
