Abstract: ObjectiveTo investigate the diagnostic value of exosomal miR-1246 for Parkinson’s disease （PD）. MethodsSerum samples were collected from 30 PD patients （PD group） and 30 healthy controls （control group） receiving physical examination in the Second Affiliated Hospital of Xinjiang Medical University from September 2022 to April 2023. The expression level of miR-1246 in exosomes was analyzed using real-time quantitative PCR. The predictive value of miR-1246 in the diagnosis of PD was assessed using the receiver operating characteristic （ROC） curves. SH-SY5Y cells were induced by 1-methyl-4-phenylpyridinium （MPP⁺） to establish a PD cell model. The optimal concentration of MPP⁺ was determined by CCK-8 assay, and the expression level of miR-1246 was verified in the MPP⁺-induced SH-SY5Y cell model. The target genes of miR-1246 were predicted using TargetScan, miRWalk, and miRase databases, and gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analysis were performed. ResultsAge and gender were matched between the PD and control groups. Compared with healthy controls, miR-1246 expression was significantly down-regulated in serum exosomes of PD patients 0.73 （0.20, 1.21） vs. 2.21 （1.00, 3.05）, P < 0.05. ROC curve analysis showed that the area under the ROC curve （AUC） of miR-1246 was 0.88 with a 95% CI of 0.77-0.99. When the cutoff value was 0.98（optimum cutoff value）, the sensitivity was calculated as 76.74% and the specificity was 95.00%. GO enrichment analysis indicated that the mechanism of action of target genes was involved with cellular junction assembly, cellular response to peptide hormones, GABA synapses, post-synaptic membranes, and transcriptional coactivator protein binding. KEGG signaling pathway was involved with glycoprotein pathway, PI3K-AKT signaling pathway, longevity regulation pathway, dopaminergic synapses, and RAS signaling pathway in cancer. In the MPP⁺-induced SH-SY5Y cell model, miR-1246 expression was significantly down-regulated compared with the control group （2.16±1.69 vs. 22.18±6.18, P < 0.05）. ConclusionsThe expression level of miR-1246 is down-regulated in serum exosomes of PD patients and in PD cell models. ROC curve analysis confirms the predictive value of miR-1246 in the diagnosis of PD, suggesting that it may serve as a potential biomarker for PD.