Soluble PDGFRβ (sPDGFRβ) is released into the bloodstream upon pericyte damage, serving as a peripheral indicator of blood-brain barrier (BBB) pericyte coverage loss. Elevated plasma sPDGFRβ correlates with BBB leakage and cognitive decline trajectories. The mechanism involves ADAM10/ADAM17-mediated ectodomain shedding of PDGFRβ from damaged pericytes. This hypothesis has the strongest evidence base with human validation in Alzheimer's disease (AD) and vascular dementia cohorts. Specificity concerns regarding peripheral PDGFRβ+ cell sources (vascular smooth muscle cells, hepatic stellate cells) are addressable through cell-type-specific validation studies and parallel peripheral biomarker controls.
Curated pathway from expert analysis
flowchart TD A["Pericyte injury"] B["ADAM10 and ADAM17 activation"] C["PDGFRbeta ectodomain shedding"] D["Soluble PDGFRbeta release"] E["Plasma sPDGFRbeta elevation"] F["BBB pericyte coverage loss"] G["Blood-brain barrier leakage"] H["Cognitive decline"] I["Neurodegeneration"] J["AD and vascular dementia progression"] K["sPDGFRbeta as peripheral biomarker"] L["ADAM10 and ADAM17 inhibition"] M["Pericyte protection strategies"] A --> B --> C --> D --> E E --> F F --> G G --> H H --> I I --> J E --> K L --> B M --> A style A fill:#ef5350,color:#0d0d1a style B fill:#4fc3f7,color:#0d0d1a style C fill:#4fc3f7,color:#0d0d1a style D fill:#4fc3f7,color:#0d0d1a style E fill:#4fc3f7,color:#0d0d1a style F fill:#ef5350,color:#0d0d1a style G fill:#ef5350,color:#0d0d1a style H fill:#ef5350,color:#0d0d1a style I fill:#ef5350,color:#0d0d1a style J fill:#ef5350,color:#0d0d1a style K fill:#81c784,color:#0d0d1a style L fill:#81c784,color:#0d0d1a style M fill:#81c784,color:#0d0d1a
No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for PDGFRΒ yet. Search RCSB →
Median TPM across 13 brain regions for PDGFRβ from GTEx v10.
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.
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 sPDGFRβ is a pericyte-loss biomarker, then declining sPDGFRβ over time will indicate improving pericyte function and better clinical outcomes in intervention studies targeting pericyte health (e.g. | In pericyte-targeting trial (e.g.,Subjects receiving BMP4 or RA derivative vs placebo), plasma sPDGFRβ decreases in treatment arm (>30% reduction at 6 months) a | — no observation — | pending | 0.74 |
| If circulating sPDGFRβ reflects pericyte loss, then sPDGFRβ levels will correlate with BBB leakage (Qalb, DCE-MRI Ktrans), decrease in brain pericyte coverage (postmortem histology), and predict cogni | In matched cohort (n≥60 with PET amyloid/tau, DCE-MRI, plasma sPDGFRβ), high plasma sPDGFRβ (top quartile) associates with elevated Qalb (OR>3), reduced pericyt | — no observation — | pending | 0.79 |