通过综合分析鉴定认知功能的新生物标志物。

IF 3.1 3区 医学 Q2 NEUROSCIENCES
Ruxue Mao, Shuoyan Zhao, Jiajie Chen, Luyao Wang, Kai Zheng, Bin Li
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引用次数: 0

摘要

认知功能障碍与各种疾病及其生物标志物的相关性已经得到了广泛的研究。然而,关注与认知功能相关的生物标志物的研究仍然有限。本研究旨在识别与认知功能相关的潜在生物标志物,并通过体外和体内实验对其进行验证,以弥补目前的研究空白。我们采用GWAS、PWAS和TWAS分析,结合孟德尔随机化和共定位分析,从欧洲队列中识别潜在的认知功能相关生物标志物。采用Aβ25-35寡聚物在SH-SY5Y和BV2细胞中建立阿尔茨海默病(AD)细胞模型,购买APP/PS1 (AD小鼠模型)。利用RT-qPCR和western blotting技术,评估AD细胞和小鼠模型中潜在生物标志物的mRNA和蛋白表达水平。采用免疫荧光法评价这些生物标志物在阿尔茨海默病细胞中的荧光表达,采用免疫组织化学法评价阿尔茨海默病模型小鼠背外侧前额皮质的染色强度。确定了三种与认知功能相关的潜在生物标志物:GPX1、CSE1L和SULT1A1。KEGG富集分析表明,GPX1、CSE1L和SULT1A1参与多种代谢途径,包括肌萎缩性侧索硬化症和亨廷顿病信号通路。RT-qPCR和western blotting结果显示,在AD细胞和小鼠模型中GPX1和CSE1L低表达,SULT1A1高表达。免疫荧光和免疫组织化学进一步证实了这些发现,在AD细胞和小鼠模型中显示出相似的表达模式。GPX1、CSE1L和SULT1A1作为认知功能的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of novel biomarkers for cognitive function via an integrative analysis.

Cognitive dysfunction associated with various diseases and its biomarkers have been extensively studied. However, research focusing on biomarkers related to cognitive function remains limited. This study aims to identify potential biomarkers associated with cognitive function and validate them through in vitro and in vivo experiments to address the current research gaps. We employed GWAS, PWAS, and TWAS analyses, combined with Mendelian randomization and colocalization analysis, to identify potential cognitive function-related biomarkers from European cohorts. An Alzheimer's disease (AD) cell model was established in SH-SY5Y and BV2 cells using Aβ25-35 oligomers, and an APP/PS1 (AD mouse model) was purchased. The mRNA and protein expression levels of potential biomarkers were assessed in AD cells and mouse models using RT-qPCR and western blotting. Immunofluorescence was used to evaluate the fluorescence expression of these biomarkers in the AD cells, while immunohistochemistry was employed to assess staining intensity in the dorsolateral prefrontal cortex of AD model mice. Three potential biomarkers associated with cognitive function were identified: GPX1, CSE1L, and SULT1A1. KEGG enrichment analysis indicated that GPX1, CSE1L, and SULT1A1 are involved in various metabolic pathways, including those related to amyotrophic lateral sclerosis and Huntington's disease signaling. RT-qPCR and western blotting revealed low expression of GPX1 and CSE1L, and high expression of SULT1A1 in both AD cells and mouse models. These findings were further confirmed by immunofluorescence and immunohistochemistry, which demonstrated similar expression patterns in the AD cell and mouse models. GPX1, CSE1L, and SULT1A1 serve as biomarkers of cognitive function.

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来源期刊
Journal of Alzheimer's Disease
Journal of Alzheimer's Disease 医学-神经科学
CiteScore
6.40
自引率
7.50%
发文量
1327
审稿时长
2 months
期刊介绍: The Journal of Alzheimer''s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer''s disease. The journal publishes research reports, reviews, short communications, hypotheses, ethics reviews, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer''s disease.
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