🧪
hypothesis

Blood-Brain Barrier Pericyte-to-Mesenchymal Transition Drives Vascular Collapse

Hypothesis

Blood-Brain Barrier Pericyte-to-Mesenchymal Transition Drives Vascular Collapse

Pericyte-to-fibroblast transition contributes to BBB breakdown and impairs glymphatic clearance.
🧬 PDGFRβ, SNAI2/SLUG, AQP4🩺 neurodegeneration🎯 Composite 56%💱 $0.54▼3.6%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates 3 support 3 oppose
✓ All Quality Gates Passed
Mechanistic 0.55 (15%) Evidence 0.62 (15%) Novelty 0.68 (12%) Feasibility 0.50 (12%) Impact 0.58 (12%) Druggability 0.48 (10%) Safety 0.52 (8%) Competition 0.50 (6%) Data Avail. 0.58 (5%) Reproducible 0.52 (5%) KG Connect 0.50 (8%) 0.560 composite
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arXiv PreprintNeurIPSNature MethodsPLOS ONE
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Composite56%

🧪 Overview

Pericyte-to-fibroblast transition contributes to BBB breakdown and impairs glymphatic clearance. Chronic PDGFRβ signaling triggers pericytes to undergo partial endothelial-mesenchymal transition. These transition-state pericytes lose coverage but gain contractile apparatus, compressing capillaries and reducing cerebral blood flow while impairing AQP4 polarisation necessary for glymphatic clearance.

🧬 Mechanism

No curated mechanism pathway recorded for this hypothesis.

⚖️ Evidence

⚖️ Evidence Matrix3 supports3 contradicts
Supports
PDGFRβ+ pericyte coverage reduced in AD
PMID:28798045
Supports
APOE4 carriers show increased BBB breakdown
PMID:29404389
Supports
AQP4 mispolarization in AD impairs glymphatic clearance
PMID:29107325
Contradicts
Hypothesis conflates EndMT (endothelial) with pericyte-to-fibroblast transition (different processes)
PMID:31340976
Contradicts
PDGFRβ is required for pericyte recruitment during development—how does same pathway become harmful?
PMID:28798045
Contradicts
Human brain lacks prominent periarterial spaces—glymphatic contribution to Aβ clearance in humans is debated
PMID:29107325
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — PDGFRΒ

No curated PDB or AlphaFold mapping for PDGFRΒ yet. Search RCSB →

💉 Clinical Trials

No clinical trials data linked to this hypothesis yet.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for PDGFRβ, SNAI2 →

No DepMap CRISPR Chronos data found for PDGFRβ, SNAI2.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

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💾 Resource Usage

No resource usage or linked notebooks recorded for this hypothesis yet.

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