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

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.

Keywords:

• Alzheimer’s disease
• early-onset Alzheimer’s disease
• late-onset Alzheimer’s disease
• serum
• exosome
• microRNA

Data Sharing Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to containing information that could compromise the privacy of research participants.

Ethics Statement

Clinical experiment protocols were approved by the Xiangya Hospital of Central South University.

Acknowledgments

The authors want to acknowledge the study participants for their dedication to the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflict of interests.

Additional information

Funding

This study is funded by the Hunan Provincial Health Commission (B202303106781).