New models to understand vascular dementia

Disintegration of the cerebrovascular matrisome: a central mechanism leading to small vessel disease and vascular cognitive impairment (Joint funding with Stroke Association and Alzheimer's Society for Advancing Care and Treatment of Vascular Dementia (ACT-VAD))

Professor Karen Horsburgh from the University of Edinburgh is studying cerebral small vessel disease (SVD), which causes about a quarter of strokes and is a leading cases of vascular dementia. Currently we do not understand what causes SVD or how to treat it. In this project, jointly funded by the BHF, the Stroke Association and the Alzheimer’s Society, Professor Horsburgh will lead a programme of work to develop new disease models of SVD. The team will focus on a part of the brain they believe has a crucial role in SVD and vascular dementia, called the neurovascular unit, which is supported by ‘scaffolding’ proteins in the brain called the extracellular matrix. In this project, the team wants to understand how a faulty gene called COL4 affects the scaffolding matrix and the neurovascular unit, and how it causes stroke and cognitive impairment. The team will use stem cells from skin samples donated by patients with a faulty COL4 gene and make them into the cells of the neurovascular unit. The team will also study an animal model with faulty COL4 that develops strokes. These models will help us better understand what causes SVD by identifying the earliest molecular changes that happen in the cells and could also reveal new ways to screen drugs to prevent or treat this disease.