Unraveling the transcriptomic landscape of brain vascular cells in dementia: A systematic review

Abstract

INTRODUCTION: Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics-driven research has revealed associations between vascular abnormalities and transcriptomic alterations in brain vascular cells, particularly endothelial cells (ECs) and pericytes (PCs). However, the impact of these molecular changes on dementia remains unclear. METHODS: We conducted a comparative analysis of gene expression in ECs and PCs across neurodegenerative conditions, including Alzheimer's disease (AD), Huntington's disease, and arteriovenous malformation, utilizing transcriptomic data from published postmortem human tissue studies. RESULTS: We identified differentially expressed genes (DEGs) consistently dysregulated in ECs and PCs across these pathologies. Notably, several DEGs are linked to vascular cell zonation and genetic risks for AD and cerebral small vessel disease. DISCUSSION: Our findings provide insights into the cellular and molecular mechanisms underlying vascular dysfunction in dementia, highlight the knowledge gaps, and suggest potential novel vascular therapeutic targets, including genes not previously investigated in this context. Highlights: Systematic review of differentially expressed genes (DEGs) in vascular cells from neurodegenerative single-nuclear RNA-sequencing (snRNA-seq) studies. Identify overlapping DEGs in multiple vascular cell types across studies. Examine functional relevance and associations with genetic risk for common DEGs. Outline future directions for the vascular omics field.