ID: h-SDA-2026-04-26-gap-20260426-001521-04-
Hypothesis
Elevated Circulating sPDGFRβ Reflects Early Pericyte Loss Preceding Neurodegeneration
Pericyte degeneration in neurodegeneration leads to proteolytic shedding of the PDGFRβ ectodomain.
neurodegeneration
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
Pericyte degeneration in neurodegeneration leads to proteolytic shedding of the PDGFRβ ectodomain. Soluble PDGFRβ (sPDGFRβ) enters peripheral circulation and may serve as an early, blood-based biomarker reflecting pericyte coverage decline before significant neuronal loss. However, peripheral sources (vascular smooth muscle, fibroblasts) significantly confound interpretation, limiting specificity for brain pericyte pathology.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["PDGFRB<br/>Pericyte Marker"]
B["Soluble PDGFRbeta<br/>Circulating Form"]
C["Pericyte<br/>Damage Signal"]
D["BBB<br/>Permeabilization"]
E["Neurovascular<br/>Dysfunction"]
F["Early Neurodegeneration<br/>Prodromal Signal"]
G["Biomarker<br/>Blood Panel"]
A --> B
B --> C
C --> D
D --> E
E --> F
A --> G
F --> G
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7⚖️ Evidence
⚖️ Evidence Matrix3 supports3 contradicts
Supports
Pericyte deficiency in AD mouse models increases BBB breakdown with reduced microvascular coverage
Supports
CSF sPDGFRβ elevation correlates with BBB breakdown in human aging and AD, predicting cognitive decline
Contradicts
Peripheral PDGFRβ expression in cardiovascular tissue could confound circulating levels
📖 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.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Volatility
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Events (7d)
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▼4.1%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we measure circulating sPDGFRβ via ELISA in early Alzheimer's disease (preclinical/prodromal stages, CDR 0-0.5) compared to age-matched cognitively normal controls, THEN we expect significantly ele | Elevated plasma sPDGFRβ (≥30% above control mean) in preclinical AD group at baseline, with the elevation preceding measurable NfL/tau increases by ≥12 months | — no observation — | pending | 0.52 |
| IF we perform selective brain pericyte ablation using pharmacological PDGFRβ inhibition (imatinib, 50mg/kg/day for 4 weeks) in C57BL/6 mice versus peripheral smooth muscle cell injury (wire injury to | Brain-specific pericyte injury model: sPDGFRβ elevated ≥40% vs. vehicle, brain NG2+ pericytes reduced ≥30% by IHC; Peripheral injury model: no significant chang | — no observation — | pending | 0.48 |
🔮 Falsifiable Predictions (2)
pendingconf 52%
IF we measure circulating sPDGFRβ via ELISA in early Alzheimer's disease (preclinical/prodromal stages, CDR 0-0.5) compared to age-matched cognitively normal controls, THEN we expect significantly elevated sPDGFRβ levels (≥30% increase, p<0.05) in the AD group reflecting early pericyte loss, BEFORE
Predicted outcome: Elevated plasma sPDGFRβ (≥30% above control mean) in preclinical AD group at baseline, with the elevation preceding measurable NfL/tau increases by ≥1
Falsification: No significant difference in sPDGFRβ between groups, or sPDGFRβ elevation correlating positively only with established neurodegeneration markers (NfL, tau) rather than preceding them, or higher sPDGFR
pendingconf 48%
IF we perform selective brain pericyte ablation using pharmacological PDGFRβ inhibition (imatinib, 50mg/kg/day for 4 weeks) in C57BL/6 mice versus peripheral smooth muscle cell injury (wire injury to femoral artery) without CNS involvement, THEN brain pericyte ablation should produce elevated plasma
Predicted outcome: Brain-specific pericyte injury model: sPDGFRβ elevated ≥40% vs. vehicle, brain NG2+ pericytes reduced ≥30% by IHC; Peripheral injury model: no signifi
Falsification: Peripheral smooth muscle injury produces equivalent or greater sPDGFRβ elevation compared to brain pericyte ablation, indicating systemic sources confound brain-specific detection; OR brain pericyte a
▸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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