Brain Pericytes is an important cell type in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Brain pericytes are perivascular cells embedded in the basement membrane of cerebral microvessels. They play critical roles in maintaining blood-brain barrier (BBB) integrity, regulating cerebral blood flow, and supporting neuronal function.
| Property |
Value |
| Location |
Cerebral microvasculature, embedded in basement membrane |
| Marker Genes |
PDGFRB, NG2 (CSPG4), CD13 (ANPEP) |
| Developmental Origin |
Mesodermal, neural crest cells contribute to some pericytes |
| Key Functions |
BBB maintenance, blood flow regulation, angiogenesis |
¶ Anatomy and Distribution
Pericytes surround cerebral capillaries and precapillary arterioles, with their somata positioned along the vessel wall. They extend numerous processes that wrap around the endothelial tube, forming peg-and-socket junctions that allow direct communication with endothelial cells.
In the human brain, pericyte coverage varies by vessel type:
- Capillaries: 80-90% coverage
- Precapillary arterioles: 60-80% coverage
- Postcapillary venules: 20-40% coverage
This coverage density correlates with BBB tightness, with higher pericyte density corresponding to stricter barrier properties.
¶ Blood-Brain Barrier Maintenance
Pericytes are essential for BBB formation and maintenance through multiple mechanisms:
- Induction of endothelial tight junctions: Pericyte-derived signals (e.g., ANG1, TGF-β) enhance tight junction protein expression (claudin-5, occludin, ZO-1)
- Transport regulation: Pericytes regulate endothelial transporter expression, limiting paracellular and transcellular leak
- basement membrane formation: Pericytes contribute to the neurovascular unit basement membrane components
Pericytes are the primary regulators of capillary blood flow in the brain. They possess contractile machinery (actin-myosin) and respond to neural activity by dilating or constricting capillaries, matching blood flow to metabolic demand.
¶ Angiogenesis and Vascular Stability
During development and in response to injury, pericytes:
- Support new vessel formation
- Stabilize nascent blood vessels
- Guide endothelial sprouting
Pericyte dysfunction contributes to AD pathogenesis through multiple pathways:
- BBB breakdown: Pericyte loss leads to increased BBB permeability, allowing peripheral proteins (e.g., albumin) into the brain
- Amyloid clearance: Pericytes participate in amyloid-β clearance via LRP1-mediated transport; pericyte dysfunction impairs this clearance
- Cerebral amyloid angiopathy (CAA): Pericyte involvement in Aβ deposition around cerebral vessels
- Hypoperfusion: Reduced pericyte-mediated vasodilation contributes to chronic hypoperfusion, a risk factor for AD
Studies show 30-50% pericyte loss in AD brains, correlating with cognitive decline.
Pericyte alterations in PD include:
- BBB permeability: Postmortem studies show increased perivascular leak in PD substantia nigra
- α-Synuclein interactions: Pericytes can take up extracellular α-synuclein, potentially contributing to propagation
- Mitochondrial dysfunction: Pericytes show mitochondrial abnormalities in PD models
In ALS, pericytes:
- Exhibit reduced coverage of motor cortex capillaries
- Show compromised BBB integrity
- May contribute to motor neuron vulnerability through vascular mechanisms
While primarily an autoimmune demyelinating disease, pericyte dysfunction:
- Contributes to lesion formation
- Impairs repair mechanisms
- Affects immune cell trafficking
- Enhancing pericyte function: Compounds that boost pericyte survival and function (e.g., PDGFRβ agonists)
- Improving amyloid clearance: Enhancing pericyte-mediated Aβ transport
- BBB protection: Preventing pericyte loss in early disease stages
Pericyte-derived factors in cerebrospinal fluid (CSF) may serve as biomarkers:
- PDGFRB levels correlate with BBB integrity
- NG2 proteoglycan fragments indicate pericyte injury
The study of Brain Pericytes 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.
- Bell et al., Pericytes control key neurovascular functions and neuronal progenitor cell migration in the brain (2010)
- Zlokovic, Neurovascular pathways to neurodegeneration in Alzheimer's disease (2011)
- Sweeney et al., Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises (2016)
- Montagne et al., Pericyte degeneration underlies white matter lesion vasculopathy in fibrous white matter disease (2015)