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.
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:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for PDGFRB yet. Search RCSB →
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.
No resource usage or linked notebooks recorded for this hypothesis yet.
| 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 |