Integrated Blood Panel of sPDGFRβ, sTM, and Circulating microRNA-320 Predicts Preclinical BBB Dysfunction
🧪 Overview
No single biomarker fully captures the heterogeneity of early BBB dysfunction across neurodegeneration subtypes. A composite scoring algorithm integrating sPDGFRβ (pericyte integrity), soluble thrombomodulin (endothelial damage, sTM), and blood microRNA-320 family members (regulators of pericyte-endothelial crosstalk and tight junction proteins) may establish a robust preclinical 'vascular impairment index.' This panel would be most informative in early/late mild cognitive impairment where intervention potential is highest. The multimodal approach reduces individual biomarker limitations but increases assay complexity and validation burden.
🧬 Mechanism
Curated pathway from expert analysis
flowchart TD
A["PDGFRbeta<br/>Platelet-Derived Growth Factor"]
B["THBD (Thrombomodulin)<br/>Endothelial Marker"]
C["Pericyte<br/>Stress Signal"]
D["Circulating<br/>Microvesicles"]
E["Blood-Brain Barrier<br/>Breakdown"]
F["Neurovascular<br/>Uncoupling"]
G["Neuroinflammation<br/>Progression"]
H["Cognitive<br/>Decline"]
A --> C
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style B fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — PDGFRΒ
No curated PDB or AlphaFold mapping for PDGFRΒ yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for PDGFRβ, THBD, mir320a/b/c from GTEx v10.
💉 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 PDGFRβ, THBD, mir320a.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we measure integrated z-scores of sPDGFRβ, sTM, and miR-320a/b/c in plasma from 200 early MCI participants and 100 cognitively normal controls, THEN the composite panel will discriminate cases from | Composite 'vascular impairment index' AUC ≥ 0.80 for early MCI vs controls; each single-marker AUC must be ≤ 0.65 | — no observation — | pending | 0.55 |
| IF we stratify 150 early MCI participants by high vs low composite panel scores and follow them with annual 3T MRI hippocampal volumetry and fluid cognition testing over 36 months, THEN high-score ind | High-score group: ≥0.9%/year hippocampal volume loss; Low-score group: ≤0.6%/year; Progression HR ≥ 1.8 | — no observation — | pending | 0.45 |
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |