Interplay between brain pericytes and endothelial cells in dementia

Dementia is becoming an increasingly important disease due to an aging population and limited treatment options. Cerebral small vessel disease (cSVD) and Alzheimer’s disease (AD) are the two most common causes of dementia with vascular dysfunction being a large component of both their pathophysiologies. The neurogliovascular unit (NVU), and in particular the blood-brain barrier (BBB) are required for maintaining brain homeostasis. A complex interaction exists between the endothelial cells, which line the blood vessels and pericytes, which surround them in the NVU. Disruption of the BBB occurs in dementia precipitating cognitive decline. In this review, we highlight how dysfunction of the endothelial-pericyte crosstalk contributes to dementia, focusing on cSVD and AD. This review examines how loss of pericyte coverage occurs and subsequent downstream changes. Furthermore, it examines how disruption to intimate crosstalk between endothelial cells and pericytes leads to alterations in cerebral blood flow, transcription, neuroinflammation and transcytosis contributing to breakdown of the BBB. This review illustrates how cumulation of loss of endothelial-pericyte crosstalk is a major driving force in dementia pathology.