Sewell Michael, Fialova Nela, Montagne Axel
UK Dementia Research Institute at the University of Edinburgh, Edinburgh, UK.
British Heart Foundation - UK Dementia Research Institute Centre for Vascular Dementia Research at the University of Edinburgh, Edinburgh, UK.
Alzheimers Dement. 2025 Feb;21(2):e14512. doi: 10.1002/alz.14512. Epub 2025 Jan 14.
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.
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.
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.
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.
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.
脑血管功能障碍在痴呆症及相关神经退行性疾病的发病机制中起着关键作用。最近由组学驱动的研究揭示了脑血管细胞，特别是内皮细胞（ECs）和周细胞（PCs）的血管异常与转录组改变之间的关联。然而，这些分子变化对痴呆症的影响仍不清楚。
我们利用已发表的死后人体组织研究的转录组数据，对包括阿尔茨海默病（AD）、亨廷顿舞蹈病和动静脉畸形在内的神经退行性疾病中的内皮细胞和周细胞的基因表达进行了比较分析。
我们确定了在这些病理学中内皮细胞和周细胞中持续失调的差异表达基因（DEGs）。值得注意的是，几个差异表达基因与血管细胞分区以及AD和脑小血管疾病的遗传风险有关。
我们的研究结果为痴呆症中血管功能障碍的细胞和分子机制提供了见解，突出了知识空白，并提出了潜在的新型血管治疗靶点，包括在此背景下以前未研究过的基因。
对神经退行性单核RNA测序（snRNA-seq）研究中血管细胞差异表达基因（DEGs）的系统综述。确定跨研究中多种血管细胞类型中的重叠差异表达基因。检查常见差异表达基因的功能相关性及其与遗传风险的关联。概述血管组学领域的未来方向。
