Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer's disease

Animal Model Exp Med. 2021 Jun 9;4(3):233-242. doi: 10.1002/ame2.12175. eCollection 2021 Sep.

Abstract

Background: Alzheimer's disease (AD) is an incurable and irreversible neurodegenerative disease, without a clear pathogenesis. Therefore, identification of candidates before amyloid-β plaque (Aβ) deposition proceeds is of major significance for earlier intervention in AD.

Methods: To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model, microRNAs (miRNAs) from urinary exosomes in 1-month-old pre-Aβ accumulation 5XFAD mice models and their littermate controls were profiled by microarray analysis. The differentially expressed miRNAs were further analyzed via droplet digital PCR (ddPCR).

Results: Microarray analysis demonstrated that 48 differentially expressed miRNAs (18 upregulated and 30 downregulated), of which six miRNAs - miR-196b-5p, miR-339-3p, miR-34a-5p, miR-376b-3p, miR-677-5p, and miR-721 - were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.

Conclusions: Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified. These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.

Keywords: 5XFAD mouse model; Alzheimer's disease; biomarkers; miRNA; microarray; urinary exosome.