Interplay between Brain Pericytes and Endothelial Cells in Dementia
Open accessAbstract
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.
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Mounting evidence suggests vascular pathologic mechanisms are involved in development of AD.
“In recent years, mounting evidence suggested that vascular pathologic mechanisms are involved in the development of AD.133”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [133]
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- Authors
- Procter, T. V., Williams, A., & Montagne, A.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- UK Dementia Research Institute (GB)
- Corresponding author
- Montagne, Axel
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 191
- Issue
- 11
- Pages
- 1917-1931
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC12179519
- OpenAlex
- W3186085265
- Cited by
- 106
- References
- 122
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 23 · 2023: 24 · 2022: 12 · 2021: 4
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Funders
- Medical Research Council (MR/T015594/1)
- Multiple Sclerosis Society (203913/Z/16/Z)
- Alzheimer’s Research UK
- Alzheimer's Society
- UK Dementia Research Institute
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- pericytes, endothelial cells, dementia, cerebral small vessel disease, Alzheimer's disease, blood-brain barrier, pericyte coverage, cerebral blood flow, neuroinflammation, transcytosis, vascular dysfunction, cognitive decline
- MeSH terms
- Alzheimer Disease, Animals, Blood-Brain Barrier, Brain, Cell Communication, Dementia, Humans, Pericytes, Endothelial Cells, Cerebral Small Vessel Diseases
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