Pericyte-endothelial cross-talk failure leads to MMP9-mediated BBB disruption and tau propagation. Single-nucleus data reveals pericytes downregulate PDGFRB and CLDN5, while endothelial cells lose TJP1 (ZO-1) expression, correlating with elevated MMP9 in neutrophils and microglia.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
MMP9["MMP9"] -->|causes| BBB_breakdown["BBB breakdown"]
MMP9_1["MMP9"] -->|causes| Tau_Propagation["Tau Propagation"]
MMP9_2["MMP9"] -->|mediates| Basement_membrane_degrada["Basement membrane degradation"]
MMP9_3["MMP9"] -->|causes| BBB_disruption["BBB disruption"]
style MMP9 fill:#ce93d8,stroke:#333,color:#000
style BBB_breakdown fill:#4fc3f7,stroke:#333,color:#000
style MMP9_1 fill:#ce93d8,stroke:#333,color:#000
style Tau_Propagation fill:#4fc3f7,stroke:#333,color:#000
style MMP9_2 fill:#4fc3f7,stroke:#333,color:#000
style Basement_membrane_degrada fill:#4fc3f7,stroke:#333,color:#000
style MMP9_3 fill:#4fc3f7,stroke:#333,color:#000
style BBB_disruption fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 MMP9.
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 pericyte-specific PDGFRB is genetically restored via AAV-PDGFRB delivery to 10-month-old C57BL/6 mice with laser-induced BBB disruption THEN MMP9 activity in cortical neutrophils/microglia will dec | ≥50% reduction in MMP9 activity (gelatin zymography); ≥60% recovery of TJP1+ endothelial cells; ≥35% decrease in plasma tau | — no observation — | pending | 0.55 |
| IF selective MMP9 inhibitor (3 mg/kg, i.p., daily) is administered to aged APP/PS1 mice (12-month-old) for 8 weeks THEN serum tau species (tau 181, tau 217) will decrease by ≥40% and BBB integrity mar | ≥40% reduction in circulating p-tau181 and p-tau217; ≥30% improvement in BBB integrity metrics | — no observation — | pending | 0.65 |