Brain endothelium: a nexus for cerebral small vessel disease

A focal point for vascular signallingBrain endothelial cells (BECs) have unique roles in controlling cerebral blood flow (CBF) and as a cornerstone of the blood-brain barrier (BBB).For example, they influence baseline CBF and act as sensors of moment-to-moment changes in neural activity.They participate in vascular remodelling and regulate immune cell interactions, thereby contributing to the maintenance of brain homoeostasis.Despite such advances, we have only scratched the surface in understanding the contribution of BECs to vascular control and subsequently brain health.Brain endothelial cells are a signalling focal point, integrating cellular, blood-borne, and mechanical stimuli.Acutely, this input is translated into electrical (ionic) or molecular signals that control vascular resistance, re-directing local CBF to regions of increased cellular activity. 1Brain endothelial cells also exert chronic effects on mural cells (pericytes and vascular muscle), glia, and neurons.Single-cell RNA sequencing (scRNAseq) studies in humans and mice have uncovered a largely unanticipated zonation-and organ-specific heterogeneity of endothelial cells, 2 the impact of which is relatively poorly defined in relation to brain health.3][4] Accounting for this heterogeneity is critical when studying cerebrovascular disease and for therapeutic targeting.As an example, the cell type expressing the most Alzheimer's disease (AD) and AD-related trait genes [based on genome-wide association studies (GWAS) in humans] is BECs.