White matter damage is a key hallmark of small vessel disease (SVD), and is correlated with cognitive decline. While we have previously shown how endothelial dysfunction drives vulnerability of myelin forming oligodendrocytes in SVD, how this vulnerability translates into myelin damage and loss is still unknown. Our research aims to better understand how white matter damage happens in SVD, with the aim of ultimately discovering pathways that could in the future be targeted to treat the disease.

We are particularly interested in the ways in which neuronal activity contributes to white matter changes in SVD, and how these white matter changes may in turn alter neuronal activity. We are also interested in the role which amyloid beta may play in mediating these interactions. Our key questions are:

1. How does neuronal activity mediate white matter damage in SVD?

2. How is neuronal activity altered in SVD?

3. How do endothelial cell-oligodendrocyte interactions affect neuronal activity?

Building on our previous work in this area we use a range of techniques, including in vivo imaging, electron microscopy, human iPSC derived cells, and human tissue to address these questions.