Objective To explore the relationship between differentially expressed miR-19b-3p and cognitive function in patients with Alzheimer's disease(AD). Methods The miRNA expression profiles of patients with AD(AD group, n=30) or healthy elderly people (NC group, n=30) were analyzed by Illumina/Solexa high-throughput sequencing technique. The miRNA lentiviral plasmids were constructed and injected into the model of AD rats. The cognitive function of rats was analyzed with water maze test. The mimics and inhibitors were synthesized and transfected into SH-SY5Y cell lines. The protein expression of β-amyloid precursor protein cleavage enzyme 1(BACE1) was detected by western blot. Results Compared with the NC group, the expression of miR-146a-5p(log2AD/Control=2.3), miR-195-5p(log2AD/Control=10.2), miR-20b-5p(log2AD/Control=15.1) in serum of AD group was up-regulated and the expression of miR-19b-3p(log2AD/Control=-8.0) and miR-125b-3p(log2AD/Control=-15.3) was down-regulated(P<0.05). Compared with the rats in the AD group((26.50±3.12)s), the rats in the AD+ miR-19b-3p group ((15.33±2.78)s) showed significantly shorter escape latencies(P<0.05). Compared with the NC group, the protein expression of BACE1 in miR-19b-3p mimetic group was decreased and the protein expression of BACE1 in inhibitor group was increased. Conclusion miR-19b-3p may improve the cognitive function of AD patients via regulating the expression of BACE1. Key words: Alzheimer's disease; Serum; miR-19b-3p; β-amyloid precursor protein cleavage enzyme 1