白质
血管性痴呆
小胶质细胞
痴呆
高强度
转录组
脑出血
神经科学
生物
疾病
病理
医学
内科学
基因表达
基因
炎症
遗传学
免疫学
磁共振成像
放射科
蛛网膜下腔出血
作者
Sebastián Díaz-Pérez,Jonathan H. DeLong,Cyprien Rivier,Chia‐Yi Lee,Michael H. Askenase,Biqing Zhu,Le Zhang,Kristen Brennand,Andrew J. Martins,Lauren Sansing
标识
DOI:10.1101/2024.12.06.627202
摘要
Abstract Vascular dementia (VaD) refers to a variety of dementias driven by cerebrovascular disease and is the second leading cause of dementia globally. VaD may be caused by ischemic strokes, intracerebral hemorrhage, and/or cerebral small vessel disease, commonly identified as white matter hyperintensities on MRI. The mechanisms underlying these white matter lesions in the periventricular brain are poorly understood. In this study we perform an extensive transcriptomic analysis on human postmortem periventricular white matter lesions in patients with VaD with the goal of identifying molecular pathways in the disease. We find increased cellular stress responses in astrocytes, oligodendrocytes, and oligodendrocyte precursor cells as well as transcriptional and translational repression in microglia in our dataset. We show that several genes identified by GWAS as being associated with white matter disease are differentially expressed in cells in VaD. Finally, we compare our dataset to an independent snRNAseq dataset of PVWM in VaD and a scRNAseq dataset on human iPSC-derived microglia exposed to oxygen glucose deprivation (OGD). We identify the increase of the heat shock protein response as a conserved feature of VaD across celltypes and show that this increase is not linked to OGD exposure. Overall, our study is the first to show that increased heat shock protein responses are a common feature of lesioned PVWM in VaD and may represent a potential therapeutic target.
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