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Differential expression of MicroRNAs in Alzheimer’s disease: a systematic review and meta-analysis

Molecular Psychiatry volume 27, pages 2405–2413 (2022)Cite this article

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A Correction to this article was published on 08 April 2022

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Abstract

Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

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Fig. 1: Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart.
Fig. 2: Forest plot for random-effects meta-analysis and important functions of miRNAs.
Fig. 3: Schematic diagram of miRNA and their pathogenesis in Alzheimer’s disease.
Fig. 4: Functional enrichment analysis results.

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Acknowledgements

This paper demonstrates independent research and all authors are acknowledged for their contributions to this study.

Author information

Author notes

  1. These authors contributed equally: Sojung Yoon, Sung Eun Kim.

Authors and Affiliations

  1. Yonsei University College of Medicine, Seoul, Republic of Korea

    Sojung Yoon, Sung Eun Kim & Sung Hwi Hong

  2. Division of Biomedical Engineering, Hankuk University of Foreign Studies, Kyoungki-do, Republic of Korea

    Younhee Ko

  3. College of Medicine, Gyeongsang National University, Jinju, Republic of Korea

    Gwang Hun Jeong

  4. Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea

    Keum Hwa Lee & Jae Il Shin

  5. Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

    Jinhee Lee

  6. Department of Psychiatry, University of Ottawa, Ontario, ON, Canada

    Marco Solmi

  7. Department of Mental Health, The Ottawa Hospital, Ontario, ON, Canada

    Marco Solmi

  8. Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, ON, Canada

    Marco Solmi

  9. School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Marco Solmi

  10. Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France

    Louis Jacob

  11. Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain

    Louis Jacob & Ai Koyanagi

  12. Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK

    Lee Smith

  13. Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan

    Andrew Stickley

  14. Stockholm Center for Health and Social Change (SCOHOST), Södertörn University, Huddinge, Sweden

    Andrew Stickley

  15. Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada

    Andre F. Carvalho

  16. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Andre F. Carvalho

  17. Pain and Rehabilitation Centre and Department of Health, Medicine and Caring Sciences, Linkoping University, Linkoping, Sweden

    Elena Dragioti

  18. Department of Medicine, University of Cambridge, Cambridge, UK

    Andreas Kronbichler

  19. ICREA, Pg. Lluis Companys 23, Barcelona, Spain

    Ai Koyanagi

  20. Centre of Chronic Illness and Ageing, University of Greenwich, London, UK

    Trevor Thompson

  21. Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, CA, 90015, USA

    Hans Oh

  22. Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Gonzalo Salazar de Pablo, Joaquim Radua & Paolo Fusar-Poli

  23. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Gonzalo Salazar de Pablo

  24. Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain

    Gonzalo Salazar de Pablo

  25. Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain

    Joaquim Radua

  26. Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden

    Joaquim Radua

  27. Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

    Paolo Fusar-Poli

  28. OASIS service, South London and Maudsley NHS Foundation Trust, London, UK

    Paolo Fusar-Poli

  29. National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK

    Paolo Fusar-Poli

Authors
  1. Sojung Yoon
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  2. Sung Eun Kim
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  3. Younhee Ko
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  4. Gwang Hun Jeong
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  5. Keum Hwa Lee
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  6. Jinhee Lee
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  7. Marco Solmi
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  8. Louis Jacob
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  9. Lee Smith
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  15. Sung Hwi Hong
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  16. Trevor Thompson
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  17. Hans Oh
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  19. Joaquim Radua
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  20. Jae Il Shin
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  21. Paolo Fusar-Poli
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Contributions

SY and JIS designed the study. SY, SUK and JIS searched the literature, and extracted data. Any discrepancies were resolved via discussion between SY, SUK and JIS. SY, SUK, YK, GHJ, KHL and JIS undertook the statistical analyses and interpreted the data. SY and SUK made the figures and tables. All authors drafted and critically revised the manuscript. All authors approved the final version of the manuscript for publication.

Corresponding author

Correspondence to Jae Il Shin.

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The authors declare no competing interests.

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The original online version of this article was revised: In this article the affiliation details for Author JAE IL SHIN were incorrectly given as ‘Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea’ but should have been ‘Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea’.

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Yoon, S., Kim, S.E., Ko, Y. et al. Differential expression of MicroRNAs in Alzheimer’s disease: a systematic review and meta-analysis. Mol Psychiatry 27, 2405–2413 (2022). https://doi.org/10.1038/s41380-022-01476-z

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