Spatial redistribution of GFAP from astrocyte end-feet to soma — not upregulation — is the mechanistically relevant BBB-dysfunction event, detectable as altered plasma/CSF GFAP ratio and AQP4 depolarization before reactive gliosis onset.
Curated pathway from expert analysis
flowchart TD
A["Astrocyte End-Foot GFAP Network<br/>Perivascular Cytoskeleton"]
B["AQP4 Polarization and Claudin-5 Support<br/>BBB Interface Integrity"]
C["Stress-Driven GFAP Redistribution<br/>End-foot to Soma Shift"]
D["Barrier Support Failure<br/>Neurovascular Coupling Weakens"]
E["Plasma GFAP/S100B Rise<br/>Early BBB Dysfunction Readout"]
F["Pre-symptomatic Neurodegeneration Signal<br/>Astrovascular Injury Window"]
A --> B
C -.->|"disrupts"| B
B --> F
C --> D
D --> E
E --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for 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 GFAP.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF acute BBB dysfunction is driven by GFAP redistribution from astrocyte end-feet to soma (rather than GFAP upregulation), THEN measuring serial plasma/CSF GFAP ratios in traumatic brain injury patien | CSF GFAP concentration will decrease by ≥30% relative to plasma GFAP within 48 hours, yielding a plasma/CSF ratio >2.0 (vs healthy ratio ~1.0-1.5), with the rat | — no observation — | pending | 0.68 |
| IF AQP4 depolarization co-occurs mechanistically with GFAP end-foot redistribution as a unitary BBB dysfunction event, THEN double-immunostaining for GFAP and AQP4 in postmortem human brain tissue fro | Quantitative microscopy will reveal AQP4 end-foot coverage per vessel decreases from baseline ~85% to <30% with concurrent soma accumulation, detectable in per- | — no observation — | pending | 0.72 |