Identification of Shared Genes between Cerebral Small Vessel Disease and Alzheimer's Disease through Multi-Omics Analyses

Abstract

Background: Cerebral small vessel disease (CSVD) and Alzheimer's disease are common causes of cognitive impairment and dementia. While previous studies have reported epidemiological associations between the two conditions, the molecular mechanisms underlying their connection remain unclear.

Methods: We conducted multi-omics analyses of gene expression profiles from CSVD and AD patients. Specifically, we performed differential expression analysis, functional enrichment analysis, and integrated analysis on four datasets comprising a total of 70 samples from GSE. Significant findings were validated in an independent dataset. Protein sequence conservation was also analyzed.

Results: A set of 16 genes exhibited consistent expression changes across the datasets, including upregulation of SMAD2, CCNA2, BAG2 and downregulation of GRM5, SLC8A3. These genes are involved in pathways such as protein degradation, tau protein binding, and calcium signaling, suggesting shared pathological processes. Validation in an independent cohort confirmed differential expression of 11 out of the 16 genes. Further, protein sequence alignment showed high conservation.

Conclusion: By leveraging multi-omics techniques, we have uncovered 16 candidate genes that may underlie both CSVD and AD. Our findings provide new insights into the molecular connection between the two conditions and pave the way for follow-up studies exploring the pathogenic roles and therapeutic potential of these shared targets.

Keywords:Cerebral Small Vessel Disease, Alzheimer's Disease, Gene expression analyses, Multi-Omics Analyse, Identification of Shared Genes