阿尔茨海默病血清外泌体miRNA生物标志物的筛选研究

段贤; 郑庆; 梁力晖; 周琳

doi:10.16016/j.2097-0927.202311088

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阿尔茨海默病血清外泌体miRNA生物标志物的筛选研究

临床医学 | 更新时间：2026-01-09

- 阿尔茨海默病血清外泌体miRNA生物标志物的筛选研究
- Screening of serum exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease
- 陆军军医大学学报 2024年46卷第15期页码：1803-1810
- 作者机构：
  
  1.410002 长沙，湖南省人民医院老年医学科
  2.410008 长沙，中南大学湘雅医院老年神经内科
  3.830063 乌鲁木齐，新疆医科大学第二附属医院神经内科
- 作者简介：
  
  [周琳，E-mail: zhoulin90117@sina.com ZHOU Lin, E-mail: zhoulin90117@sina.com
- 基金信息：
  
  新疆神经系统疾病研究重点实验室开放课题(XJDX1711-2214)
- DOI：10.16016/j.2097-0927.202311088
  中图分类号： Q522;R446.119;R745.7
- 收稿：2023-11-18，
  
  修回：2023-12-12，
  
  纸质出版：2024-08-15
- 稿件说明：
移动端阅览
段贤, 郑庆, 梁力晖, 等. 阿尔茨海默病血清外泌体miRNA生物标志物的筛选研究[J]. 陆军军医大学学报, 2024,46(15):1803-1810.

Xian DUAN, Qing ZHENG, Lihui LIANG, et al. Screening of serum exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease[J]. Journal of Army Medical University, 2024, 46(15): 1803-1810.
段贤, 郑庆, 梁力晖, 等. 阿尔茨海默病血清外泌体miRNA生物标志物的筛选研究[J]. 陆军军医大学学报, 2024,46(15):1803-1810. DOI： 10.16016/j.2097-0927.202311088.

Xian DUAN, Qing ZHENG, Lihui LIANG, et al. Screening of serum exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease[J]. Journal of Army Medical University, 2024, 46(15): 1803-1810. DOI： 10.16016/j.2097-0927.202311088.

摘要

目的

通过比较阿尔茨海默病(Alzheimer’s disease，AD)患者与健康对照者的血清外泌体中miRNAs的表达，筛选出差异表达的miRNAs。

方法

收集2017年3月至2018年8月就诊于中南大学湘雅医院老年神经内科的AD患者71例为研究组(AD)，健康体检者71例为对照组(HC)。各组选取4例样本行血清外泌体miRNAs高通量二代测序，检测、分析2组间差异表达的miRNAs，筛选出表达差异有统计学意义、表达量最高的前4种miRNAs，在71例AD患者和71例健康体检者样本中用实时荧光定量逆转录聚合酶链式反应(qRT-PCR)测定其相对浓度。

结果

高通量二代测序共检测到775种miRNAs，其中有44种miRNAs在2组间表达差异有统计学意义(

0.05)。与HC组相比，AD组中有34种miRNAs表达上调，10种miRNAs表达下调，其中表达量最高的前4种miRNAs为miRNA-148a-3p、miRNA-16-5p、miRNA-19b-3p、miRNA-483-5p。MiRNA-148a-3p表达在AD组中较HC组显著上调(

0.01)

但miRNA-16-5p、miRNA-19b-3p、miRNA-483-5p在2组间表达差异无统计学意义。绘制ROC曲线，miRNA-148a-3p的AUC为0.7113(95%

: 0.622~0.801)，灵感度为71.6%，特异度为69.7%。

结论

血清外泌体miRNA-148a-3p可望作为AD诊断的生物标志物。

Abstract

Objective

To screen differentially expressed miRNAs (DEMs) by comparing the expression of miRNAs in serum exosomes between Alzheimer's disease (AD) patients and healthy controls.

Methods

A total of 71 AD patients admitted to Department of Geriatric Neurology of Xiangya Hospital from March 2017 to August 2018 and another 71 healthy individuals who taking physical examination in the hospital during same period were recruited and assigned into AD and HC groups

respectively. Four AD patients and four healthy subjects were selected for high-throughput second-generation sequencing of exosome miRNAs. The results were analyzed to obtain the DEMs between them

and the top 4 DEMs were finally selected. Then real-time quantitative real-time PCR was applied for all the subjects to detect the expression of the 4 DEMs.

Results

High-throughput second-generation sequencing detected 775 miRNAs

and 44 DEMs were found with statistical difference between the 2 groups (

0.05). Compared with the HC group

34 miRNAs were up-regulated and 10 were down-regulated in the AD group. The top 4 DEMs were miRNA-148a-3p

miRNA-16-5p

miRNA-19b-3p and miRNA-483-5p. MiRNA-148a-3p was significantly up-regulated in the AD group than the HC group (

0.01)

but there were no significant differences in the expression level in the other 3 DEMs between the 2 groups. ROC curve analysis showed that the area under the curve of miRNA-148a-3p was 0.7113 (95%

: 0.622~0.801)

with a sensitivity of 71.6% and a specificity of 69.7%.

Conclusion

Serum exosome miRNA-148a-3p can be used as a biomarker for the diagnosis of AD.

关键词

Keywords

references

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