摘要Background: Alzheimer ' s disease (AD) is an incurable and irreversible neurodegen-erative 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 mi-croarray 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.