Sun Yuzhe, Hefu Zhen, Li Benchao, Lifang Wang, Zhijie Song, Zhou Li, Deng Yan, Zhili Liu, Ding Jiahong, Li Tao, Zhang Wenwei, Chao Nie, Rong Shuang
Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China.
BGI-Shenzhen, Shenzhen, China.
Research (Wash D C). 2023 Apr 13;6:0114. doi: 10.34133/research.0114. eCollection 2023.
Small extracellular vesicle (sEV) is an emerging source of potential biomarkers of Alzheimer's disease (AD), but the role of microRNAs (miRNAs) in sEV is not well understood. In this study, we conducted a comprehensive analysis of sEV-derived miRNAs in AD using small RNA sequencing and coexpression network analysis. We examined a total of 158 samples, including 48 from AD patients, 48 from patients with mild cognitive impairment (MCI), and 62 from healthy controls. We identified an miRNA network module (M1) that was strongly linked to neural function and showed the strongest association with AD diagnosis and cognitive impairment. The expression of miRNAs in the module was decreased in both AD and MCI patients compared to controls. Conservation analysis revealed that M1 was highly preserved in the healthy control group but dysfunctional in the AD and MCI groups, suggesting that changes in the expression of miRNAs in this module may be an early response to cognitive decline prior to the appearance of AD pathology. We further validated the expression levels of the hub miRNAs in M1 in an independent population. The functional enrichment analysis showed that 4 hub miRNAs might interact with a GDF11-centered network and play a critical role in the neuropathology of AD. In summary, our study provides new insights into the role of sEV-derived miRNAs in AD and suggests that M1 miRNAs may serve as potential biomarkers for the early diagnosis and monitoring of AD.
小细胞外囊泡（sEV）是阿尔茨海默病（AD）潜在生物标志物的一个新兴来源，但微小RNA（miRNA）在sEV中的作用尚未得到充分了解。在本研究中，我们使用小RNA测序和共表达网络分析对AD中sEV衍生的miRNA进行了全面分析。我们共检测了158个样本，包括48例AD患者的样本、48例轻度认知障碍（MCI）患者的样本和62例健康对照的样本。我们鉴定出一个与神经功能密切相关且与AD诊断和认知障碍关联最强的miRNA网络模块（M1）。与对照组相比，AD和MCI患者中该模块中miRNA的表达均降低。保守性分析显示，M1在健康对照组中高度保守，但在AD和MCI组中功能失调，这表明该模块中miRNA表达的变化可能是在AD病理学出现之前对认知衰退的早期反应。我们在一个独立人群中进一步验证了M1中核心miRNA的表达水平。功能富集分析表明，4个核心miRNA可能与以生长分化因子11（GDF11）为中心的网络相互作用，并在AD的神经病理学中起关键作用。总之，我们的研究为sEV衍生的miRNA在AD中的作用提供了新的见解，并表明M1 miRNA可能作为AD早期诊断和监测的潜在生物标志物。
