Identification of Hub Genes and Potential Molecular Mechanisms among Alzheimers Disease, Vascular Dementia, and Mild Cognitive Impairment by Integrated Bioinformatics Analysis

Abstract

Background: Dementia is caused by cognitive decline that interferes with daily living. It is often considered a syndrome rather than a single disease. The causes of dementia are diverse, including brain degeneration and cerebrovascular disease, but the pathogenic mechanisms remain unclear. Alzheimers disease (AD) and vascular dementia (VaD) are the most common forms of dementia. As dementia cases continue to rise worldwide, investigating dementia has become increasingly important. Early-stage AD and VaD may cause amnestic mild cognitive impairment (MCI). Therefore, elucidating the relationship among AD, VaD, and MCI is crucial. This study aimed to analyze the correlations among AD, VaD, and MCI, and differences in these three diseases using bioinformatics methods on gene expression omnibus (GEO) databases, to provide information. Methods: Gene set enrichment (GSE) 18309 and GSE122063 were utilized to identify differentially expressed mRNAs among AD, VaD, and MCI. The gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these mRNAs. Results: The main functions of the identified mRNAs were revealed, with phosphatidylinositide 3 kinases-protein kinase B (PI3K-Akt) signaling and hypoxia-inducible factor-1 (HIF-1) signaling showing the highest frequency. Conclusion: Bioinformatics analyses of public databases provide insights into the relationship and differences among AD, VaD, and MCI based on differential mRNA expression and pathway enrichment, laying the foundation for future mechanistic studies. The identified pathways such as PI3K-Akt and HIF-1 signaling represent promising targets for further investigation and therapeutic development.