Comparative Multi-Omics Analysis Identifies Shared Transcriptomic Signatures and Therapeutic Targets in Alzheimer’s, Parkinson’s, and Huntington’s Diseases

Abstract

Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) are major neurodegenerative disorders that share certain pathological features but differ in their genetic etiology and clinical presentation. Their potential molecular intersections remain incompletely understood. In this research, we conducted a comparative transcriptomic analysis using postmortem brain RNA-seq datasets from AD (GSE53697), PD (GSE68719), and HD (GSE64810) to identify shared and disease-specific transcriptional signatures. Differentially expressed genes (DEGs) were determined and functionally characterized through Gene Ontology (GO) enrichment. Protein–protein interaction (PPI) networks were generated using STRING and visualized in Cytoscape to identify central hub genes, followed by gene–disease and drug-interaction analyses to assess functional and therapeutic relevance. Ten DEGs were found to overlap among the three disorders, exhibiting variable directions of regulation across diseases. Enrichment analysis indicated convergence on immune- and inflammation-related biological processes. Key hub genes, including MMP9, LCN2, CXCL2, CCL2, S100A8, and S100A9, were identified as central nodes within the PPI network. Although the overlap in DEGs was limited, the findings suggest that neuroinflammatory signaling represents a shared molecular theme across AD, PD, and HD, warranting further validation in independent cohorts.