Cerebral small vessel disease (SVD) is a leading contributor to dementia and stroke, with pathology centred on the brain’s microvasculature. Increasing evidence highlights the role of endothelial activation, pericyte dysfunction, blood–brain barrier (BBB) dysfunction, and inflammatory responses in driving disease onset and progression. Importantly, many of these vascular mechanisms are also implicated in Alzheimer’s disease (AD), pointing to overlapping pathways of neurovascular dysfunction across dementias.

In our lab, we combine translational approaches across human and preclinical models to investigate these mechanisms. Using advanced imaging, we assessed age-related and disease-associated changes in pericyte and endothelial function in both mouse and human brain tissue. Circulating vascular biomarkers were evaluated in patient cohorts and correlated with MRI features of SVD. Complementary experimental models in mice, including endothelial- and pericyte-targeted manipulations, were used to probe causal relationships between vascular dysfunction, BBB integrity, and microglial responses.

Together, these investigations reveal the importance of endothelial–pericyte crosstalk in vascular vulnerability and highlight conserved mechanisms across species. This integrated strategy advances our understanding of SVD pathophysiology and its overlap with AD, identifying potential avenues for biomarker development and therapeutic intervention across neurodegenerative diseases.