Evaluation of Microarray-derived Gene Expression Patterns in Transgenic Mouse Models of Alzheimer’s Disease (Tau and Amyloid beta) Using Bioinformatics Tools

 The aim of this study was to compare the gene expression changes and their effects on protein networks, transcription factors prediction, cellular pathways and small RNAs in the transgenic mouse models of Alzheimer’s disease (Tau and Amyloid beta).

 The results of the brain tissue microarray data from two models of Alzheimer’s disease were analyzed in GEO database. Protein networks prediction performed using String database and analyzed by Cytoscape software. The changed genes were used for prediction of transcription factors (TFs) and cellular pathways via Enrichr web service. Moreover, the ToppGene portal was used for prediction of the role of small RNAs involved in these models.

Analysis of protein networks have showed that the CTSS gene (encode Cathepsin S), a lysosomal cysteine protease, was the key gene and the main inter-network linker in the both models. Also, the data from evaluation of TFs resulting to introduce of IRF8 genes (encode Interferon Regulatory Factor 8) and NFE2L2 (encode Nuclear Factor, Erythroid 2 Like 2) that are involved in the immune system and oxidative stress respectively. On the other hand, we have shown that let-7 small RNA, which is involved in the immune system, could act as a major regulator in these gene pathways.

 The immune system has a critical role in the both models of Alzheimer’s disease and seems that the control of the immune-related genes (IRF8 and let-7) activity besides decrease of oxidative stress (CTSS and NFE2L2) in both models is a plausible therapeutic target.