Transcriptomic and network analysis identifies shared pathways across Alzheimer's disease and vascular dementia

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Alzheimer's disease (AD) and vascular dementia (VaD) frequently co-occur, complicating diagnosis and treatment.
• Effective differential diagnosis and targeted therapies for VaD remain elusive.
• Identifying shared pathological mechanisms between AD and VaD is crucial for developing novel treatments.

Purpose of the Study:

• To analyze common differentially expressed genes (DEGs) in the temporal cortex of AD and VaD patients.
• To elucidate shared biological functions and pathways implicated in both diseases.
• To validate key gene expression changes in animal models.

Main Methods:

• Utilized gene expression array data from the GEO database.
• Performed Gene Ontology (GO) and KEGG pathway enrichment analysis.
• Conducted protein-protein interaction (PPI) analysis and validated mRNA expression via RT-qPCR in AD and VaD mice.

Main Results:

• Identified 143 common DEGs between AD and VaD.
• Common DEGs are primarily involved in chemical synaptic transmission, neuroactive ligand-receptor interactions, and cytokine-cytokine receptor interactions.
• Downregulation of GABBR1 and upregulation of IL-17RA, IL-17, and IL-18 mRNA were confirmed in AD and VaD models.

Conclusions:

• Confirmed shared genetic underpinnings between AD and VaD.
• Highlighted critical genes and pathways linking these neurodegenerative diseases.
• Provided a theoretical basis and potential drug targets for combined AD and VaD therapies.