In this study, identified the DEGs and the communal DEGs. The co-DEGs may be the key factor in the two diseases. For in-depth analysis and a higher likelihood of the data, we screening of functional an pathway annotation of significant DEGs. Actin filament may be play a critical role in the AD and T2DM.The actin cytoskeleton facilitates participate in the insulin signaling pathway. Alzheimer’s disease can be leaded by the actin filament disassembly in dendritic spines. Numerous studies suggested that a functional role for the actin filament in the AD and T2DM. Moreover, the peripheral insulin resistance impact brain insulin resistance, which are the key factor influencing of AD. It is possible that obese patients with aging and aging-related neurodegenerative diseases have a higher level of insulin resistance .
In depth analysis of the DEGs with the two diseases, which screened 30 hub genes. A higher score indicates a higher likelihood of the prediction being true. The hub genes were subjected to GO and KEGG pathway enrichment analysis. We found that the majority of the results of enrichment analysis was about autophagy. Many studies show that autophagy deficits leaded to the early stage of AD and the drugs related to autophagy may be the new target for AD. There is associated with improvements in insulin resistance, which have been demonstrated by the autophagy-lysosome pathway. Metformin, as the first choice in T2DM, is may have a protective effect on T2DM patients by autophagy pathway. And metformin reduces the symptoms in mouse models of AD. This means that metformin have the therapeutic potential for AD.
The top 5 hub genes(TP53,PINK1,SNCA,MAP1LC3A,PIK3CA) were determined on PPI basis. These genes are associated with autophagy-related genes. TP53 regulates autophagy of cytoplasmic and nuclear. Previous studies have shown that TP53 plays an important role in autophagy. However, much of the existing published literature consists of studies were associated with tumors. PINK1 suggests mitophagy to mediate autophagy . Many studies showed that SNCA content effect in causing Parkinson disease (PD). And some factors may induce autophagy, regulation of SNCA expression levels is linked to the development of neuropathology. MAP1LC3A was one of the biomarker for the cellular autophagy. We can testing of MAP1LC3A expression indicate autophagy. PIK3CA/AKT signaling pathway is a upstream effector of the mTOR pathway, which mainly regulate autophagy. Much of studies suggested that these genes and T2DM-rerelated AD were linked to the autophagy. One of the genes may be the key factor of the two diseases or demonstrate the gene-disease associations. These hub genes may be the potential biomarkers targets for the two diseases.
There are some limitations of this study. First, the sample number in this study was small. Second, we need a verification test to confirm the reliably of the DEGs and the hub nodes.Additionally, more in vitro and in vivo verification tests are needed to confirm the meanings and functions