Transcriptomic analysis identifies shared biological foundations between ischemic stroke and Alzheimer's disease.

Area of Science:

• Neurology and Genomics
• Immunology
• Transcriptomics

Background:

• Alzheimer's disease (AD) and ischemic stroke (IS) are significant neurological disorders with suspected clinical and pathophysiological links.
• Previous research has explored potential genetic mechanisms connecting AD and IS, but a clear understanding remains elusive.

Purpose of the Study:

• To investigate the shared genetic underpinnings and biological pathways between Alzheimer's disease and ischemic stroke.
• To identify common hub genes, drug targets, and potential therapeutic strategies for both neurological conditions.

Main Methods:

• Transcriptomic analysis of peripheral whole blood gene expression datasets from AD patients, IS patients, and healthy controls.
• Identification of differentially expressed genes (DEGs), shared biological pathways, and hub genes using protein-protein interaction (PPI) network analysis.
• Evaluation of immune cell proportions in peripheral blood using CIBERSORT and correlation analysis with gene expression.

Main Results:

• Identified 74 shared DEGs and 18 shared biological processes between AD and IS, including nine immune-related pathways.
• Discovered five significant hub genes and eight potential drug target genes associated with both diseases.
• Observed an increased proportion of M0 macrophages in the peripheral circulation of both AD and IS patients, with significant correlation to SOD1 expression.

Conclusions:

• The study suggests a potential shared etiology between AD and IS, with the immune system, particularly M0 macrophage elevation, playing a crucial role.
• Identified shared hub genes, therapeutic gene targets, and candidate drugs offer promising avenues for developing novel treatment strategies for both AD and IS.