Plasma Extracellular Vesicle MicroRNA Analysis of Alzheimer's Disease Reveals Dysfunction of a Neural Correlation Network

Yuzhe Sun; Zhen Hefu; Benchao Li; Wang Lifang; Song Zhijie; Li Zhou; Yan Deng; Liu Zhili; Jiahong Ding; Tao Li; Wenwei Zhang; Nie Chao; Shuang Rong

doi:10.34133/research.0114

Plasma Extracellular Vesicle MicroRNA Analysis of Alzheimer's Disease Reveals Dysfunction of a Neural Correlation Network

Research (Wash D C). 2023 Apr 13:6:0114. doi: 10.34133/research.0114. eCollection 2023.

Authors

Yuzhe Sun^{1

2

3}, Zhen Hefu^{2

3}, Benchao Li¹, Wang Lifang^{2

3}, Song Zhijie^{2

4}, Li Zhou¹, Yan Deng¹, Liu Zhili^{2

4}, Jiahong Ding^{2

3}, Tao Li², Wenwei Zhang^{2

3}, Nie Chao^{2

3}, Shuang Rong¹

Affiliations

¹ Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China.
² BGI-Shenzhen, Shenzhen, China.
³ Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen 518120, China.
⁴ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

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.