Objective · To analyze the expression profile of plasma microRNA (miRNA) in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by bioinformatics method, and explore its pathogenesis at the level of genetic regulation. Methods · Five MCI patients due to AD and five control participants were recruited. The plasma miRNA expression profiles were analyzed by miRNA microarray sequencing. Target genes of significantly up-regulated miRNAs were detected by TargetScan 7.2 database. The miRNA-gene interaction network of significantly up-regulated miRNAs was established by Cytoscape software, and the key miRNAs of the network were analyzed. The target genes of key miRNAs were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis using R packages. Results · There are 13 up-regulated miRNAs in the plasma of MCI patients due to AD, and 5 of them were key miRNAs in miRNA-gene interaction network. Target genes of these miRNAs were mainly involved in biological process such as synaptic plasticity regulation, Wnt signaling pathway, synaptic vesicle transport and synaptic vesicle localization, as well as Ras signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway and glycolysis/gluconeogenesis pathway. Conclusion · Five up-regulated miRNAs in plasma of MCI due to AD may be the main regulators involved in the pathological mechanism of AD, which can be used as potential biomarkers for diagnosis of MCI due to AD.