A longitudinal biomarker panel centered on plasma GFAP can distinguish harmful mechanisms from protective adaptation. The decisive experiment is to measure plasma GFAP before and after endothelial exosome profiling in stratified models.
Curated pathway from expert analysis
flowchart TD
A["Pericyte Stress<br/>PDGFR-beta Signaling Loss"]
B["Astrocyte Reactivity<br/>A1 Pro-Inflammatory Polarization"]
C["GFAP Upregulation<br/>Intermediate Filament Assembly"]
D["GFAP Release<br/>Plasma Biomarker Elevation"]
E["BBB Disruption<br/>Endothelial-Pericyte Uncoupling"]
F["SASP and Complement<br/>S100B and C1q Secretion"]
G["Neuronal Vulnerability<br/>Synapse Loss"]
A --> E
B --> C
C --> D
E --> B
E --> F
F --> G
D -.->|"biomarker of"| G
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style C fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style D fill:#1b5e20,stroke:#81c784,color:#81c784
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo curated PDB or AlphaFold mapping for PLASMA yet. Search RCSB →
Median TPM across 13 brain regions for plasma GFAP 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 plasma GFAP.
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 GFAP reflects harmful BBB-linked astrocyte activation, THEN BBB-stabilizing treatment in a pericyte-stress mouse model will lower plasma GFAP by >=20% within 8 weeks. | BBB stabilization reduces plasma GFAP >=20% and improves tracer leakage >=25% versus vehicle. | — no observation — | pending | 0.52 |
| IF plasma GFAP separates causal BBB injury from compensation, THEN GFAP will rise by >=15% only in participants with concurrent pericyte-stress extracellular vesicle signatures over 12 months. | GFAP annual increase >=15% is enriched in the high pericyte-stress EV group with odds ratio >=2.0. | — no observation — | pending | 0.57 |