The relationship between the aberrant long non-coding RNA-mediated competitive endogenous RNA network and Alzheimer's disease pathogenesis

In this research, we investigated the abnormal expression of lncRNA and established lncRNA-associated ceRNA regulatory networks composed of potential therapeutic targets in AD based on RNA sequencing (RNA-seq) analysis and experimental verification. RNA-seq was performed in the cerebral cortex and hippocampus of 5×FAD mice of AD to systematically investigate altered lncRNA-associated ceRNA regulatory network, along with qualitative analyses for key differentially expressed lncRNAs, miRNAs, and mRNAs involved. The results showed that 7 lncRNAs were significantly altered in the cortex and hippocampus of 5×FAD mice compared with WT mice. The potential functions of differentially expressed genes were highly correlated with learning and memory activities and the pathogenesis of AD. Furthermore, lncRNA Xist and highly correlated miRNAs and mRNAs were identified as key mediators of pathophysiological processes in AD. Our findings illustrated the AD-derived lncRNA-mediated ceRNA network, accompanied by aberrant expression involved in the pathological gene networks, which may contribute to understanding the pathological mechanism of AD and provide potential therapeutic targets for drug development. Three 7-month-old 5 × FAD mice of C57BL/6J genetic background and their non-transgenic mice (WT mice) of the same month of age were grouped. Each group consisted of two females and one male (n = 3 per group). The cerebral cortex and hippocampus were taken from each mouse, for a total of 12 samples.