Pericyte Loss In Neurodegeneration is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Pericytes are mural cells embedded in the basement membrane of cerebral microvessels, playing crucial roles in maintaining blood-brain barrier (BBB) integrity, regulating cerebral blood flow, and supporting neuronal health. Pericyte loss is increasingly recognized as a key early event in the pathogenesis of Alzheimer's disease (AD), vascular cognitive impairment, and other neurodegenerative disorders[1].
Pericytes are strategically positioned at the neurovascular unit, where they communicate with endothelial cells, astrocytes, and neurons. Their processes ensheath capillaries and pre-capillary arterioles, making them essential for proper cerebral microcirculation and BBB function.
Amyloid-beta toxicity: Aβ directly damages pericytes through:
Tau pathology: Pathological tau in pericytes disrupts their function
Chronic hypoperfusion: Reduced blood flow creates pericyte stress
Aging: Normal aging is associated with pericyte decline[5]
The study of Pericyte Loss In Neurodegeneration has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Winkler EA, Nishida Y, Sagare AP, et al. Pericyte loss in Alzheimer's disease. Acta Neuropathol. 2015;129(4):469-490. DOI:10.1007/s00401-014-1379-9
Bell RD, Winkler EA, Sagare AP, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and in brain diseases. Neuron. 2010;68(3):409-427. DOI:10.1016/j.neuron.2010.09.023
Sengillo JD, Winkler EA, Walker CT, et al. Deficiency in mural vascular cells coincides with blood-brain barrier breakdown in Alzheimer's disease. Brain Pathol. 2013;23(3):303-310. DOI:10.1111/bpa.12004
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci. 2011;12(12):723-738. DOI:10.1038/nrn3114
Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in aging and Alzheimer's disease. Ann Neurol. 2015;78(5):821-831. DOI:10.1002/ana.24511
Sagare AP, Bell RD, Zhao Z, et al. Pericyte-secreted IGF2 contributes to the development of neurovascular dysfunction in diabetes. Nat Commun. 2013;4:2437. DOI:10.1038/ncomms3437
Armulik A, Genové G, Mäe M, et al. Pericytes regulate the blood-brain barrier. Nature. 2010;468(7323):557-561. DOI:10.1038/nature09522
Nakamura K, Arimura K, Chaboub S, et al. Metabolic dysfunction in pericytes: Implications for blood-brain barrier dysfunction in Alzheimer's disease. J Cereb Blood Flow Metab. 2021;41(9):2157-2172. DOI:10.1177/0271678X21998904
Van De Haar HJ, Burgmans S, Jansen JF, et al. Blood-brain barrier leakage in patients with early Alzheimer disease. Radiology. 2016;281(2):527-535. DOI:10.1148/radiol.2016152244
Hall CN, Reynell C, Gesslein B, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(7494):55-60. DOI:10.1038/nature13028
🔴 Low Confidence
| Dimension | Score |
|---|---|
| Supporting Studies | 10 references |
| Replication | 0% |
| Effect Sizes | 25% |
| Contradicting Evidence | 0% |
| Mechanistic Completeness | 75% |
Overall Confidence: 39%