Lee Jibeom, Park Suhyeon, Kim Yumin, Kim Hyun Min, Oh Chang-Myung
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
J Lipid Atheroscler. 2022 May;11(2):133-146. doi: 10.12997/jla.2022.11.2.133. Epub 2021 Jul 27.
Alzheimer's disease (AD) is the most common cause of dementia. The statins have shown beneficial effects on cognitive functions and reduced the risk of dementia development. However, the exact mechanisms of statin effects in AD are not yet fully understood. In this study, we aimed to explore the underlying mechanisms of statin on AD.
We downloaded AD blood dataset (GSE63060) and statin-related blood gene expression dataset (GSE86216). Then we performed gene expression analysis of each dataset and compared blood gene expressions between AD patients and statin-treated patients. Then, we downloaded mouse embryonic neural stem cell dataset (GSE111945) and performed gene expression analysis.
From the human blood dataset, we identified upregulated/downregulated genes in AD patients and statin-treated patients. Some of the upregulated genes (, , ) in the blood of AD patients are downregulated in statin-treated patients. Several downregulated genes (, , , , and ) are upregulated in statin-treated patients. Gene set enrichment analysis using mouse stem cell dataset revealed a significant relationship of Kyoto Encyclopedia of Genes and Genomes-defined pathway of AD in statin-treated neural stem cells compared to vehicle-treated neural stem cells (normalized enrichment score: -2.24 in male and -1.6 in female).
These gene expression analyses from human blood and mouse neural stem cell demonstrate the important clues on the molecular mechanisms of impacts of statin on AD disease. Further studies are needed to investigate the exact role of candidate genes and pathways suggested in our AD pathogenesis study.
阿尔茨海默病（AD）是痴呆最常见的病因。他汀类药物已显示出对认知功能有益，并降低了痴呆发生的风险。然而，他汀类药物在AD中的确切作用机制尚未完全明确。在本研究中，我们旨在探索他汀类药物对AD作用的潜在机制。
我们下载了AD血液数据集（GSE63060）和他汀类药物相关血液基因表达数据集（GSE86216）。然后我们对每个数据集进行基因表达分析，并比较AD患者和接受他汀类药物治疗患者之间的血液基因表达。接着，我们下载了小鼠胚胎神经干细胞数据集（GSE111945）并进行基因表达分析。
从人类血液数据集中，我们鉴定出AD患者和接受他汀类药物治疗患者中上调/下调的基因。AD患者血液中一些上调基因（……）在接受他汀类药物治疗的患者中下调。一些下调基因（……）在接受他汀类药物治疗的患者中上调。与用载体处理的神经干细胞相比，使用小鼠干细胞数据集进行的基因集富集分析显示，在接受他汀类药物治疗的神经干细胞中，京都基因与基因组百科全书定义的AD通路存在显著关联（标准化富集分数：雄性为-2.24，雌性为-1.6）。
这些来自人类血液和小鼠神经干细胞的基因表达分析揭示了他汀类药物对AD疾病影响的分子机制的重要线索。需要进一步研究来调查我们AD发病机制研究中提出的候选基因和通路的确切作用。
