The discovery of disrupted gene expression in vascular dementia and disease-associated cell types

What is it about?

Vascular dementia is the second most prevalent type of dementia. It is the accumulation of vascular lesions in the subcortical white matter, which progress into adjacent brain. However, there is neither direct medical therapy nor a comprehensive understanding of the underlying mechanisms of this disease. The current study used brain tissue from vascular dementia patients and healthy controls, and analyzed the gene expression differences in the cell types of the white matter in the lesion, adjacent to the lesion and in control, using single nucleus RNA sequencing. We find distinct patterns of gene expression in vascular dementia white matter across all cell types of this region. There are distinct clusters of microglial and endothelial cells that suggest molecular pathways for disease progression and also disease repair.

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Photo by Steven HWG on Unsplash

Photo by Steven HWG on Unsplash

Why is it important?

For the first time, we investigated the gene expression changes in all the cell types in human vascular dementia. We found that vascular dementia is associated with disruptions in angiogenesis, immune response, and myelination. As endothelial cells are a particular focus of vascular dementia pathological progression, we identified 3 subtypes of endothelial cells in vascular dementia, in which one subtype (e2) only exists in the vascular dementia lesion and adjacent tissue, and shows significant interrupted function in vascular regeneration. The major deregulated e2 genes are validated in RNA level using quantitative PCR and protein expression using immunohistochemistry. In a summary, our findings help us understand the comprehensive picture of how cell functions are dysregulated during vascular dementia, which provide important information for the further study of the disease and the development of novel therapeutic targets.

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