A cellular atlas of regional neurovascular vulnerability and neurodegeneration

Blood vessels deliver nutrients and remove waste from the brain. The neurogliovascular unit (NGVU) is critical to regulating and maintaining these homeostatic processes.

NGVU dysfunction is prominent across neurodegenerative diseases including Alzheimer disease, with clear regional vulnerabilities.

Our NGVU knowledge is limited by our ability to isolate the individual cellular components, to understand how they vary by brain region, how they change during disease, and how changes in the NGVU affect the parenchyma.

DRI/DPUK groups together developed a new method for isolating both highly-enriched NGVU and parenchymal fractions from the same sample, to deliver contemporaneous gene expression profiles of each cell type.

Using our expertise in brain single cell transcriptomics, we will create an atlas of regional NGVU variation and its relationship to the parenchymal state in vascular neurodegeneration focussing on cerebral small vessel disease.

While of huge value to the international neurovascular community, it will also enable us to unravel regional cell-type-specific effects of genetic risk and risk factor effects, to improve current in vitro and in vivo NGVU models, and most importantly, to identify new therapeutic targets for cerebral small vessel disease, a core vascular cause of neurodegeneration and dementia for which there is currently no effective therapy.