Screening of Akt and Wnt Pathways for the Early Diagnosis and Treatment of Alzheimer's Disease

Abstract

Abstract Background Alzheimer's disease is a neurodegenerative disease that is difficult to reverse. Akt and Wnt play a role in complex cellular signaling, which is important for studying the onset of AD. This study aimed to screen key genes of the Akt and Wnt pathways as potential biomarkers for the early diagnosis and treatment of AD. Methods We searched for differentially expressed genes in the GEO database, constructed candidate gene protein-protein interaction (PPI) networks, and used least absolute shrinkage and selection operator (LASSO) regression analysis and the support vector machine-recursive feature elimination (SVM-RFE) algorithm to screen for key genes. Correlation and functional similarity analyses of key genes, immune infiltration analysis, ceRNA network construction, and drug prediction of key genes were performed. We further validated the expression of key genes in streptozotocin (STZ)-treated AD mice using quantitative reverse transcription (RT-q) PCR. Results Bioinformatic analysis identified five key genes in AD, including PRKACA, CDH3, ATP6V0C, DLL1, and CELSR2. Step-down tests, immunohistochemistry, and silver plate staining confirmed the success of STZ-induced AD in mice. RT-PCR showed that the relative expression of DLL1 mNRA in the AD group was higher than that in the control group, whereas the relative expression of ATP6V0C and PRKACA mRNA in the AD group was lower than the control group, which was consistent with the results of the bioinformatic analysis. Conclusions This study provides a basis for a more comprehensive understanding of the underlying mechanisms of AD. Furthermore, DLL1, ATP6V0C, and PRKACA may be potential intervention targets for AD.