Serum Exosomal miRNA-125b and miRNA-451a are Potential Diagnostic Biomarker for Alzheimer’s Diseases

IF 2.1 Q3 CLINICAL NEUROLOGY Degenerative neurological and neuromuscular disease Pub Date : 2024-04-01 DOI:10.2147/DNND.S444567
Xian Duan, Qing Zheng, Lihui Liang, Lin Zhou
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Abstract

Aim To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer’s disease (AD) based on the expression of miRNAs in AD patients. Methods We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1–67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways.
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血清外泌体 miRNA-125b 和 miRNA-451a 是阿尔茨海默病的潜在诊断生物标记物
目的 探讨血清外泌体 miRNA 的诊断价值,并根据 AD 患者体内 miRNA 的表达预测其靶基因在阿尔茨海默病(AD)中的作用。方法 我们通过高通量二代测序和实时定量 PCR 测定外泌体 miRNA 的相对浓度。结果 收集了 71 例 AD 患者和 71 例 ND 受试者。研究表明,与健康受试者相比,hsa-miR-125b-1-3p、hsa-miR-193a-5p、hsa-miR-378a-3p、hsa-miR-378i和hsa-miR-451a在AD患者的血清外泌体中有不同程度的表达。根据 ROC 分析,hsa-miR-125b-1-3p 在 AD 组与健康组相比的 AUC 为 0.765,灵敏度和特异性分别为 82.1%-67.7% 。对其靶基因的富集分析表明,这些基因与神经活性配体-受体相互作用、PI3K-Akt 信号通路、Hippo 信号通路和神经系统相关通路有关。而且,hsa-miR-451a的AUC为0.728,其区分AD组与健康组的敏感性和特异性分别为67.9%和72.6%。对其靶基因的富集分析表明,它与细胞因子-细胞因子受体相互作用和 PI3K-Akt 信号通路有关。结论 AD 患者血清外泌体 microRNA 的失调可能有助于 AD 的诊断。miRNAs的靶基因可能通过不同途径参与AD的发生和发展。
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