OBJECTIVE To evaluate the effect of microRNA on memory impairment of chronic brain hypoperfusion (CBH)rats generated by bilateral common carotid artery occlusion (2VO).METHODS Morris water mazewas performed to evaluate cognitive ability.Expression of miR-195, BACE1 and APP in hippocampus and cortex were evaluatedafterrats performed by 2VO, injected by lentiviral vector-mediated overexpression of miR-195(lenti-pre-miR195) and/or antisense molecule (lenti-pre-AMO-miR-195).RESULTS We show here CBH significantly decreased the learning and memory ability and upregulated expression of APP and BACE1 proteins in the hippocampus and cortex of rats, as evaluated by western blot and immunofluorescence.In reciprocal, qRT-PCR analysis showed that microRNA-195(miR-195) was downregulated in both the hippooampus and cortex of rats following CBH,and in the plasma of dementia patients.APP and BACE1 proteins were downregulated by miR-195 overexpression,upregulated by miR-195 inhibition, and unchanged by binding-site mutation or miR-masks, indicating that APP and BACE1 are two potential targets for miR-195.Knockdown of endogenous miR-195 by elicited dementia in rats,whereas overexpression of miR-195 using lenti-pre-miR-195 reduced dementia vulnerability triggered by 2VO.Additionally, chromatin immunoprecipitation analysis showed that NF-κB was bound to the promoter region of miR-195 and inhibited its expression.CONCLUSION MiR-195 may play a key role in determining dementia-susceptibility in 2VO rats by regulating APP and BACE1 expression at the post-transcriptional level, and exogenous complement of miR-195 may be a potentiallyvaluable anti-dementia approach.