ID: h-SDA-2026-04-26-gap-debate-20260426-011
Hypothesis
Soluble PDGFRβ as a Peripheral Indicator of Pericyte-Mediated Blood-Brain Barrier Breakdown in Preclinical Neurodegeneration
Pericyte loss in Alzheimer's disease leads to proteolytic shedding of PDGFRβ into circulation, providing a blood-accessible marker of pericyte injury.
neurodegeneration
EvidencePending (0%)📖 8 cit🗣 1 debates✓ 8 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
Pericyte loss in Alzheimer's disease leads to proteolytic shedding of PDGFRβ into circulation, providing a blood-accessible marker of pericyte injury. Circulating PDGFRβ correlates with BBB permeability and cognitive decline. Critical weakness: PDGFRβ is not pericyte-specific (expressed on vascular smooth muscle cells, fibroblasts, hepatic stellate cells), making source attribution essential before clinical deployment.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD A["Abeta deposition"] --> B["Pericyte injury and loss"] B --> C["PDGFRbeta proteolytic shedding"] C --> D["Soluble PDGFRbeta in circulation"] D --> E["BBB permeability increase"] E --> F["Neurotoxin extravasation into CNS"] F --> G["Synapse loss and neuronal dysfunction"] G --> H["Cognitive decline"] B --> I["PDGFRbeta polymorphisms increase AD risk"] J["Therapeutic: PDE3A inhibition"] --> K["Enhanced pericyte survival"] K --> B D --> L["Source attribution challenge (VSMC, fibroblasts, hepatic stellate cells)"] L -.-> H style A fill:#ef5350,stroke:#c62828,color:#fff style B fill:#ef5350,stroke:#c62828,color:#fff style C fill:#4fc3f7,stroke:#0288d1,color:#000 style D fill:#4fc3f7,stroke:#0288d1,color:#000 style E fill:#ef5350,stroke:#c62828,color:#fff style F fill:#ef5350,stroke:#c62828,color:#fff style G fill:#ef5350,stroke:#c62828,color:#fff style H fill:#ffd54f,stroke:#f9a825,color:#000 style I fill:#ef5350,stroke:#c62828,color:#fff style J fill:#81c784,stroke:#388e3c,color:#000 style K fill:#81c784,stroke:#388e3c,color:#000 style L fill:#ffd54f,stroke:#f9a825,color:#000
⚖️ Evidence
⚖️ Evidence Matrix8 supports3 contradicts
Supports
Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders.
Supports
Blood-Brain Barrier Breakdown in Alzheimer's Disease: Mechanisms and Targeted Strategies.
Contradicts
PDGFRβ+ perivascular fibroblasts distinct from pericytes complicate pericyte-specific attribution
Contradicts
Pericyte coverage changes in aging are highly variable and don't always correlate with cognitive outcomes
Contradicts
AD risk association was modest (OR ~1.3) and not replicated in independent cohorts
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — PDGFRB
No curated PDB or AlphaFold mapping for PDGFRB 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.
No DepMap CRISPR Chronos data found for PDGFRB (Platelet-Derived Growth Factor Receptor Beta).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Falling
7d Momentum
▼ 1.2%
Volatility
Medium
0.0291
Events (7d)
3
Price History
▼15.6%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
🔎 Predictions vs Observations1 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If soluble PDGFRβ in plasma reflects pericyte degeneration, then sPDGFRβ will correlate with the rate of BBB integrity decline (DCE-MRI Ktrans slope) and with cognitive deterioration rate, independent | In a 2-year longitudinal AD cohort (n≥100 with amyloid PET, DCE-MRI, and plasma sPDGFRβ), baseline sPDGFRβ in top tertile predicts accelerated Ktrans decline (> | — no observation — | pending | 0.78 |
🔮 Falsifiable Predictions (1)
pendingconf —
If soluble PDGFRβ in plasma reflects pericyte degeneration, then sPDGFRβ will correlate with the rate of BBB integrity decline (DCE-MRI Ktrans slope) and with cognitive deterioration rate, independent of amyloid plaque burden and brain atrophy.
Predicted outcome: In a 2-year longitudinal AD cohort (n≥100 with amyloid PET, DCE-MRI, and plasma sPDGFRβ), baseline sPDGFRβ in top tertile predicts accelerated Ktrans
Falsification: sPDGFRβ does not predict BBB decline rate or cognitive trajectory after adjustment for amyloid and atrophy; pericyte marker changes are secondary to neurodegeneration markers, not independent drivers.
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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