Genetic insights and molecular pathways in Alzheimer's disease: Unveiling the complexity of neurodegeneration

• This study provides a comprehensive molecular analysis of Alzheimer's disease (AD) through differential gene expression profiling, highlighting key dysregulated genes and pathways involved in disease progression. • By identifying 157 up-regulated and 177 down-regulated genes, including critical players like MYC, CREM, and pathways such as PI3K-Akt and Wnt signalling, this research uncovers potential molecular drivers of AD. • The integration of transcription factor and miRNA analysis further reveals novel regulatory elements that could serve as biomarkers or therapeutic targets. • These findings enhance our understanding of the complex molecular mechanisms underlying AD and offer promising avenues for future therapeutic interventions. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the accumulation of amyloid-beta plaques and tau tangles in the brain. We conducted a comprehensive Differential Gene Expression (DGE) analysis using RNA sequencing and microarray datasets from the Gene Expression Omnibus (GEO) database to elucidate the molecular mechanisms underlying AD. Forty-three datasets, encompassing 902 samples from various biological sources, were analysed. The study identified 157 frequently upregulated and 177 down-regulated genes associated with AD. Upregulated genes include DDX3Y, H6PD and KIF1B , while down-regulated genes include CREM, CD44, and HES4. Functional enrichment analysis using Enrichr revealed significantly upregulated pathways, including the PI3K-Akt signalling and Wnt signalling pathways. The downregulated pathways include the immune system and TNF signalling pathway. Network analysis with STRING identified key interactive genes, including MYC, HSP90AB1 and CENPA among the upregulated genes, and ENO1, RPLP0 , and RPS3A among down-regulated genes. Additionally, the research focused on identifying transcription factors and miRNAs associated with AD, revealing critical regulatory elements influencing disease progression. These findings provide insights into the dysregulated pathways, key genes, and regulatory mechanisms involved in AD, offering potential targets for therapeutic intervention.