阿尔茨海默病中的外泌体微小RNA生物标志物：系统评价与荟萃分析

Exosomal microRNA biomarkers in Alzheimer's disease: Systematic review and meta-analysis.

作者信息

Liu Shiyu, Zhao Min, Yang Xin, Liu Yuan, Xu Hongcai, Yan Huayu, Xu Yumin

机构信息

Department of Encephalopathy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China; The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China.

Department of Encephalopathy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China; Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Zhengzhou, China.

出版信息

Clin Chim Acta. 2025 Aug 7;578:120542. doi: 10.1016/j.cca.2025.120542.

DOI:10.1016/j.cca.2025.120542

PMID:40783152

Abstract

BACKGROUND

Recent studies have suggested an association between exosomal microRNAs (miRNAs) and Alzheimer's disease (AD). However, their effectiveness as clinical biomarkers has yet to be definitively established. This study aims to assess the diagnostic value of exosomal miRNAs in AD through a meta-analysis.

METHODS

As of June 10, 2025, a comprehensive literature search was conducted across eight databases using various search strategies to identify studies that met the inclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was employed to evaluate the quality of the included studies. Threshold heterogeneity was examined using Meta-DiSc 1.4 software. Stata/MP 18.0 software was used to synthesize effect sizes, including sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). Subgroup analysis, meta-regression, and sensitivity analysis were conducted to explore potential sources of heterogeneity. Deek's funnel plot was used to assess publication bias.

RESULTS

A total of 14 articles (comprising 23 studies) were included, involving 910 patients and 696 controls. The pooled SEN, SPE, PLR, NLR, DOR, and AUC were 0.83 [95 % CI (0.77-0.88)], 0.84 [95 % CI (0.76-0.90)], 5.24 [95 % CI (3.32-8.26)], 0.20 [95 % CI (0.15-0.29)], 25.70 [95 % CI (12.79-51.62)] and 0.90 [95 % CI (0.87-0.92)], respectively. The Spearman correlation coefficient was 0.070 (P = 0.752 > 0.05), indicating an absence of threshold effect heterogeneity. The asymmetry test of Deek's funnel plot revealed no evidence of publication bias (P = 0.06 > 0.05). Subgroup analysis demonstrated enhanced diagnostic performance for AD using exosomal miRNAs in blood samples with a sample size of ≥ 50 and a specific cut-off value.

CONCLUSION

The findings of this study suggest that the expression levels of exosomal miRNAs are correlated with AD and may serve as potential diagnostic biomarkers for the disease.

摘要

背景

最近的研究表明外泌体微小核糖核酸（miRNA）与阿尔茨海默病（AD）之间存在关联。然而，它们作为临床生物标志物的有效性尚未得到明确证实。本研究旨在通过荟萃分析评估外泌体miRNA在AD中的诊断价值。

方法

截至2025年6月10日，使用各种检索策略在八个数据库中进行了全面的文献检索，以识别符合纳入标准的研究。采用诊断准确性研究质量评估-2（QUADAS-2）工具评估纳入研究的质量。使用Meta-DiSc 1.4软件检查阈值异质性。使用Stata/MP 18.0软件合成效应量，包括灵敏度（SEN）、特异度（SPE）、阳性似然比（PLR）、阴性似然比（NLR）、诊断比值比（DOR）和受试者工作特征曲线下面积（AUC）。进行亚组分析、meta回归和敏感性分析以探索异质性的潜在来源。使用Deek漏斗图评估发表偏倚。

结果

共纳入14篇文章（包括23项研究），涉及910例患者和696例对照。合并的SEN、SPE、PLR、NLR、DOR和AUC分别为0.83 [95%置信区间（CI）（0.77 - 0.88）]、0.84 [95% CI（0.76 - 0.90）]、5.24 [95% CI（3.32 - 8.26）]、0.20 [95% CI（0.15 - 0.29）]、25.70 [95% CI（12.79 - 51.62）]和0.90 [95% CI（0.87 - 0.92）]。Spearman相关系数为0.070（P = 0.752 > 0.05），表明不存在阈值效应异质性。Deek漏斗图的不对称检验未发现发表偏倚的证据（P = 0.06 > 0.05）。亚组分析表明，对于样本量≥50且有特定截断值的血液样本，使用外泌体miRNA诊断AD的性能增强。