Circulating microRNAs as potential biomarkers for the identification of vascular dementia due to cerebral small vessel disease.

Background: the diagnosis of cerebral small vessel disease, a leading cause of vascular dementia (VaD), relies solely on neuroimaging studies. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers in various disorders. Our aim was to identify differentially expressed, circulating miRNAs in small vessel VaD which could serve as diagnostic biomarkers for this disease.

Method: we performed plasma miRNA profiling by quantitative polymerase chain reaction (qPCR) array in small vessel VaD patients and age- and gender-matched, cognitively normal and healthy controls. Selected, differentially expressed miRNAs were validated by qPCR. Sensitivity, specificity and area under the curve (AUC) were calculated for each individual miRNA.

Results: profiling results showed that 44 miRNAs were differentially expressed in small vessel VaD cases (P < 0.05 with a fold change of <2 or >2). A set of seven, highly differentially expressed miRNAs (fold change of <3.6 or >3.6), were estimated in a cohort of 204 small vessel VaD patients and 200 healthy, age and gender-matched controls. Validation study revealed that four miRNAs (miR-409-3p, miR-502-3p, miR-486-5p and miR-451a) could be used as valuable biomarkers for identifying the disease. Sensitivity, specificity and AUC for these miRNAs were 76, 75, 75  and 70%; 89, 89, 83 and 75% and 0.94, 0.92, 0.90 and 0.86, respectively. However, combined receiver operating characteristic curve analysis of seven miRNAs revealed an AUC of 0.64 with sensitivity of 55.5% and specificity of 65.7%.

Conclusion: plasma miR-409-3p, miR-502-3p, miR-486-5p and miR-451a could be used to differentiate small vessel VaD patients from healthy controls. Large-scale studies of their biomarker potential are warranted.