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.
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
No 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 (Platelet-Derived Growth Factor Receptor Beta).
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 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 |