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Peripheral Blood MicroRNA Expression Profiles in Alzheimer’s Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism

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Abstract

A series of investigations have been performed regarding microRNA (miRNA, miR) of Alzheimer’s disease (AD) patients. However, most of these used microarray with neither validation by PCR nor any follow-up on the biological mechanism implicated by findings. Further, there were rarely any analyses linking clinical phenotype of de novo, drug-naive patients to cellular pathogenic mechanism(s) to date. Microarray screening followed by validation via quantitative PCR (Q-PCR) assays and the relationship between miRNAs and phenotypic indices were evaluated. Additionally, the cellular mechanism of miRNAs through effects of β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) was assessed. We identified 2 specific differentially expressed (DE) miRNAs (miR-339 and miR-425) as potential diagnostic biomarkers for AD and revealed that these DE miRNAs could be involved in modulating the pathogenesis of AD via BACE1 protein inhibition. The findings presented here reveal a detailed snapshot of the profile of peripheral blood mononuclear cells (PBMC) miRNA changes in AD patients, association with clinical phenotype, and potential roles in cellular pathogenesis.

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Acknowledgments

The authors are grateful to all of the subjects who kindly agreed to participate in this study. We also thank Dr. Lian Li at the Department of Pharmacology, Emory University School of Medicine, for critical reading and comments on this manuscript. This study was supported by the National Basic Research Development Program of China (No. 2010CB945200, 2011CB504104), and the National Natural Science Foundation of China (No. 81371218, 81001426, 81070958, 81171027, 81200842, 81573401,91332107).

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    Authors and Affiliations

    1. Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

      Ru-Jing Ren, Yi Zhou, Li-ling Wang, Sheng-Di Chen, Gang Wang & Qi Cheng

    2. Research Laboratory of Cell Regulation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

      Yong-Fang Zhang

    3. Department of Biochemistry and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, 30322, USA

      Eric B. Dammer

    4. Department of Neurology, Shanghai Putuo District People’s Hospital, Shanghai, 200060, China

      Xiao-Hong Liu

    5. Department of Neurology, Shanghai TCM-integrated Hospital, Shanghai University of TCM, Shanghai, 200082, China

      Bei-Lei Feng

    6. Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden

      Guo-Xin Jiang

    7. Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

      Sheng-Di Chen

    8. School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China

      Qi Cheng

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    1. Ru-Jing Ren
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    Correspondence to Sheng-Di Chen, Gang Wang or Qi Cheng.

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    Conflict of Interest

    The authors declare that they have no competing interests.

    Ethical Approval

    The study was approved by the Research Ethics Committee of Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine in China.

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    Written informed consent was obtained from each participant.

    Additional information

    Ru-Jing Ren and Yong-Fang Zhang contributed equally to this work.

    Electronic Supplementary Material

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    ESM 1

    Demographics of subjects in the study (DOC 34 kb)

    ESM 2

    Real-time PCR Primer used in the study (DOC 32 kb)

    ESM 3

    The correlation between DE miRNAs and clinical phenotypes among AD group (n=30) (DOC 29 kb)

    ESM 4

    Differentially Expressed miRNAs (Pass Volcano Plot) (XLS 84 kb)

    ESM 5

    Targeted gene prediction (XLS 48 kb)

    Figure S1

    MiRNAs-gene network in the present study (JPEG 71 kb)

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    Ren, RJ., Zhang, YF., Dammer, E.B. et al. Peripheral Blood MicroRNA Expression Profiles in Alzheimer’s Disease: Screening, Validation, Association with Clinical Phenotype and Implications for Molecular Mechanism. Mol Neurobiol 53, 5772–5781 (2016). https://doi.org/10.1007/s12035-015-9484-8

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