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Profiling of Serum Exosome MiRNA Reveals the Potential of a MiRNA Panel as Diagnostic Biomarker for Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the older adults. Although much effort has been made in the analyses of diagnostic biomarkers, such as amyloid-β, tau, and neurofilament light chain, identifying peripheral blood-based biomarkers is in extremely urgent need for their minimal invasiveness and more convenience. Here we characterized the miRNA profile by RNA sequencing in human serum exosomes from AD patients and healthy controls (HC) to investigate its potential for AD diagnosis. Subsequently, Gene Ontology analysis and pathway analysis were performed for the targeted genes from the differentially expressed miRNAs. These basic functions were differentially enriched, including cell adhesion, regulation of transcription, and the ubiquitin system. Functional network analysis highlighted the pathways of proteoglycans in cancer, viral carcinogenesis, signaling pathways regulating pluripotency of stem cells, and cellular senescence in AD. A total of 24 miRNAs showed significantly differential expression between AD and HC with more than ± 2.0-fold change at p value < 0.05 and at least 50 reads for each sample. Logistic regression analysis established a model for AD prediction by serum exosomal miR-30b-5p, miR-22-3p, and miR-378a-3p. Sequencing results were validated using quantitative reverse transcription PCR. The data showed that miR-30b-5p, miR-22-3p, and miR-378a-3p were significantly deregulated in AD, with area under the curve (AUC) of 0.668, 0.637, and 0.718, respectively. The combination of the three miRs gained a better diagnostic capability with AUC of 0.880. This finding revealed a miR panel as potential biomarker in the peripheral blood to distinguish AD from HC.

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Data Availability

All datasets generated or analyzed during the study are included in this published article and its supplementary information files.

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Acknowledgements

The authors would like to thank all donors and their families for the blood samples provided in the study. Without their selfless contribution, the research could not have proceeded. Furthermore, the authors thank Dr. Shan Yan for his thoughtful discussion of the manuscript.

Funding

This work was supported by Science Foundation of Shanghai Municipal Commission of Science and Technology (19ZR1439300) and Project of Shanghai Municipal Health Commission (201640131).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Jinshan Branch of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, 147 Jiankang Road, Jinshan District, Shanghai, 201599, People’s Republic of China

    Zhiwu Dong, Shuang Liang, Xianglu Liu, Feifei Li, Huiling Liu & Li Sun

  2. Shanghai Jinshan Zhongren Aged Care Hospital, Shanghai, 201501, China

    Hongjun Gu, Jian Xue & Feng Yao

  3. Department of Ultrasound Medicine, Jinshan Branch of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 201599, China

    Qiang Guo

  4. Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Kewen Zhao

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  1. Zhiwu Dong
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Corresponding author

Correspondence to Zhiwu Dong.

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Ethics Approval and Consent to Participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was obtained from the ethics committee of Jinshan Branch of Shanghai Sixth People’s Hospital. Informed consent was obtained from all individual participants and the legally authorized representatives of the AD patients included in the study.

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Supplementary Information

Supplementary Fig. 1

Mapping rate of the NGS generated reads mapped to the reference sequences for each sample. Prefix “A” indicates AD; Prefix “B” indicates HC. (PNG 210 kb)

High Resolution (TIF 94 kb)

Supplementary Table 1

All the relevant information of the detected miRNAs, including chromosome, start, end, strand, fold change, and p-value. Overall, 1957 miRNAs were detected in our study. A total of 207 miRNAs were differentially expressed in the AD compared with the HC (p-value < 0.05, and ± 1.2-fold change). (XLSX 570 kb)

Supplementary Table 2

Functional Gene Ontology (GO) analysis of genes that were targeted by these deregulated miRNAs. Biological process (BP), cellular component (CC), and molecular function (MF) terms were ranked by p-value (p-value < 0.05). (XLSX 1759 kb)

Supplementary Table 3

Functional pathway analysis of genes that were targeted by these deregulated miRNAs. The pathways were ranked by p-value (p-value < 0.05). (XLSX 103 kb)

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Dong, Z., Gu, H., Guo, Q. et al. Profiling of Serum Exosome MiRNA Reveals the Potential of a MiRNA Panel as Diagnostic Biomarker for Alzheimer’s Disease. Mol Neurobiol 58, 3084–3094 (2021). https://doi.org/10.1007/s12035-021-02323-y

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