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

Sojung Yoon, Sung Eun Kim, Younhee Ko, Gwang Hun Jeong, Keum Hwa Lee, Jinhee Lee, Marco Solmi, Louis Jacob, Lee Smith, Andrew Stickley, Andre F. Carvalho, Elena Dragioti, Andreas Kronbichler, Ai Koyanagi, Sung Hwi Hong, Trevor Thompson, Hans Oh, Gonzalo Salazar de Pablo, Joaquim Radua, Jae Il Shin*Paolo Fusar-Poli

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

16 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2405-2413
Number of pages9
JournalMolecular Psychiatry
Volume27
Issue number5
DOIs
Publication statusPublished - May 2022

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