Affiliations: [a] Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, P.R. China | [b] Department of Endocrinology, The Second Hospital of Shijiazhuang City, Shijiazhuang, P.R. China | [c] Department of Mental Health, The First Hospital of Hebei Medical University, Shijiazhuang, P.R. China | [d] Institute of Mental Health, Hebei Medical University, Shijiazhuang, P.R. China | [e] Department of Burns and Plastic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, P.R. China | [f]
Burn Engineering Center of Hebei Province, Shijiazhuang, P.R. China
Correspondence to: Shunjiang Xu, PhD, Central Laboratory, The First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang 050031, China. Tel.: +86 311 8591 7257; Fax: +86 311 8591 7290;
E-mail: [email protected].
Abstract: Evidence suggests that individuals with amnestic mild cognitive impairment (aMCI) tend to progress to probable Alzheimer’s disease (AD) with aging. This study was performed to examine whether circulating miRNAs could be potential predictors for the progression of aMCI to AD. A total of 458 patients with aMCI were included in this study, and the clinical data were collected at two time points: the baseline and the follow-up assessment. These aMCI patients were classified into two groups after 5 years: aMCI-stable group (n = 330) and AD-conversion group (n = 128). The expression of miR-206 and miR-132 and the levels of BDNF and SIRT1 in serum were detected using a quantitative real-time RT-PCR (qPCR) and the ELISA method, respectively. Kaplan-Meier method (Log-rank test) was used for univariate survival analysis. Cox proportional hazard model was used to estimate the prognostic value of miRNAs in conversion from aMCI to AD. At the baseline, serum levels of miR-206 in aMCI-AD group were significantly elevated compared to aMCI-aMCI group and the same trend was found at 5-year follow-up time point as well. There were no significant differences in serum levels of miR-132 between the conversion and non-conversion group at both time points. Kaplan-Meier analysis showed significant correlation between AD conversion and higher serum levels of miR-206 for aMCI patients (HR = 3.60, 95% CI: 2.51– 5.36, p < 0.001). Multivariate Cox regression analysis revealed that serum miR-206 and its target BDNF were significant independent predictors for AD conversion (HR = 4.22, p < 0.001). These results suggested that increased serum miR-206 level might be a potential predictor of conversion from aMCI to AD.