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

A Correction to this article was published on 08 April 2022

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

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Authors and Affiliations



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.

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Correspondence to Jae Il Shin.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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).

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