Sun Yue, Jiang Mengni, Long Xiang, Miao Yongzhen, Du Huanhuan, Zhang Ting, Ma Xuejun, Zhang Yue, Meng Hongrui
Department of Neurology, Shanghai East Hospital of Tongji University School of Medicine, Shanghai, 20092, People's Republic of China.
Institute of Neuroscience, Soochow University, Suzhou, 215123, People's Republic of China.
J Mol Neurosci. 2024 May 22;74(2):55. doi: 10.1007/s12031-024-02225-3.
The dysregulation of lipid metabolism has been strongly associated with Alzheimer's disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.
脂质代谢失调与阿尔茨海默病（AD）密切相关，且与疾病进展的各个方面有着复杂的联系，如淀粉样蛋白生成、生物能量缺陷、氧化应激、神经炎症和髓鞘变性。在此，我们对AD来源的转录组数据集中大脑和外周血中的脂质代谢基因进行了全面的生物信息学评估，描述了脂质代谢差异表达基因（DEGs）与疾病病理以及免疫细胞偏好之间的相关性。通过应用加权基因共表达网络分析（WGCNA），确定了与脂质代谢相关的模块特征基因，并对其在生物过程、分子途径中的分子功能及其与病理表型和分子网络的关联进行了表征。生物网络分析表明，神经元细胞和免疫细胞中DEGs的表达模式存在显著差异，脑组织和外周血中的细胞类型富集也存在差异。此外，还检索并评估了针对中枢和外周DEGs的药物以及血液中枢纽基因的诊断模型，其中一些被证明对治疗和诊断有用。这些结果揭示了中枢、外周和免疫细胞激活中转录异常脂质代谢的独特模式，为AD的诊断和指导更有效的治疗提供了有价值的脂质代谢见解。
