P2‐151: MICROARRAY EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS IN TRIPLE TRANSGENIC AD MOUSE BRAIN WITH OR WITHOUT INDUCED T2DM

Impaired insulin signaling and declined recognition are the features of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are abundant in the central nervous system and play a key role in brain function as well as many neurological diseases. However, the regulatory function of lncRNAs in the brain of AD with or without T2DM has not been well studied. In this study, we analyzed the expression profile of differentially lncRNAs in the AD brain with or without induced T2DM. Morris water maze (MWM) and microarray technology was used to evaluate the spatial learning and memory ability of and the expression profile of lncRNAs in the brain of 6 and 12months triple transgenic AD mouse with or without T2DM induced by high glucose and high fat feed stuff with low dose of STZ. MWM test showed that weakened the spatial learning and memory ability of AD mouse with T2DM. 3146 differentially expressed lncRNAs and 1629 differentially expressed mRNAs were identified (fold change≥2.0, p< 0.05). Among of them, 2483 lncRNAs and 1089 mRNAs was significantly aberrant expression in 6 months triple transgenic AD mice with T2DM compared to the control mice without T2DM. Whereas, only 438 lncRNAs and 275 mRNAs were identified in comparing 6 months and 12month of 3xTg AD mice with T2DM and 225 lncRNAs and 265 mRNAs in 12 months of 3xTg-AD and 3xTg-AD mice with T2DM. Gene Ontology (GO) analysis and pathway analysis showed that these lncRNAs were involved in multiple biological processes, including synaptic transmission, number of synaptic vesicle, neuropeptide disorder and inflammation relative to phagosome, TNF and NF-kappa B signaling pathway in 3xTg AD mice with T2DM. Additionally, the lncRNA-mRNA-network and TF-gene-lncRNA-network were constructed to identify core regulatory lncRNAs and transcription factors. And we discovered formyl peptide receptor 1（Fpr1）played a important role in neuroinflammation and synaptic transmission. This study for the first time represents an expression profile of differentially expressed lncRNAs in the AD brain with or without T2DM and may provide a novel point of view into the mechanisms of cognitive disorder of T2DM and AD brain.