Interplay between Brain Pericytes and Endothelial Cells in Dementia

Prevalence of dementia continues to increase because of the aging population and limited treatment options. Cerebral small vessel disease and Alzheimer disease are the two most common causes of dementia with vascular dysfunction being a large component of both their pathophysiologies. The neurogliovascular unit, in particular the blood-brain barrier (BBB), is required for maintaining brain homeostasis. A complex interaction exists among the endothelial cells, which line the blood vessels and pericytes, which surround them in the neurogliovascular unit. Disruption of the BBB in dementia precipitates cognitive decline. This review highlights how dysfunction of the endothelial-pericyte crosstalk contributes to dementia, and focuses on cerebral small vessel disease and Alzheimer disease. It also examines loss of pericyte coverage and subsequent downstream changes. Furthermore, it examines how disruption of the intimate crosstalk between endothelial cells and pericytes leads to alterations in cerebral blood flow, transcription, neuroinflammation, and transcytosis, contributing to breakdown of the BBB. Finally, this review illustrates how cumulation of loss of endothelial-pericyte crosstalk is a major driving force in dementia pathology. (Am J Pathol 2021, 191: 1917-1931; https://doi.org/10.1016/ j.ajpath.2021.07.003)

Automated summary

This review examines how dysfunction of the endothelial-pericyte crosstalk contributes to dementia, focusing on cerebral small vessel disease and Alzheimer disease. It highlights the disruption of the intimate crosstalk between endothelial cells and pericytes leading to alterations in cerebral blood flow, transcription, neuroinflammation, and breakdown of the BBB, which are major driving forces in dementia pathology.