ID: h-e9e0225d
Hypothesis
Neurovascular Permeability Score (NVPS): Composite Plasma + Imaging Biomarker Panel
A LASSO-optimized composite score integrating plasma GFAP, S100B, NFL, soluble PDGFR-β, and claudin-5 fragments to achieve AUC >0.90 for pre-symptomatic AD/PD, outperforming single-marker approaches including amyloid PET.
neurodegeneration
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 2 oppose
✓ All Quality Gates Passed
🧪 Overview
A LASSO-optimized composite score integrating plasma GFAP, S100B, NFL, soluble PDGFR-β, and claudin-5 fragments to achieve AUC >0.90 for pre-symptomatic AD/PD, outperforming single-marker approaches including amyloid PET.
🧬 Mechanism
🧬 Curated Mechanism Pathway
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:#81c784⚖️ Evidence
⚖️ Evidence Matrix5 supports2 contradicts
Supports
Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease.
Supports
Blood-based biomarkers in Alzheimer's disease - moving towards a new era of diagnostics.
Supports
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies.
Supports
GFAP as a Potential Biomarker for Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Supports
Amyloid-beta misfolding and GFAP predict risk of clinical Alzheimer's disease diagnosis within 17 years.
Contradicts
Blood GFAP changes occur across Alzheimer biomarker and all-cause dementia contexts, so GFAP alone is not specific for BBB dysfunction or astrocyte end-foot retraction.
Contradicts
Plasma biomarkers associate with both neurodegenerative atrophy and microvascular burden, complicating interpretation of GFAP as a selective neurovascular permeability readout.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — GFAP
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for GFAP from GTEx v10.
💉 Clinical Trials
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.
🏆 Tournament
🏆 Arenas / Elo
No arena matches recorded yet. Browse Arenas →
📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0774
Events (7d)
0
Price History
▼3.4%💾 Resource Usage
LLM Tokens
1,559,664
$5.2824
API Calls
260
Total Cost
$5.2824
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF the LASSO-optimized NVPS composite panel (plasma GFAP, S100B, NFL, soluble PDGFR-β, claudin-5 fragments) is applied to a pre-symptomatic AD/PD cohort at baseline, THEN the AUC for predicting conver | AUC >0.90 for NVPS panel in pre-symptomatic AD/PD prediction | — no observation — | pending | 0.45 |
| IF NVPS composite score is directly compared head-to-head against plasma GFAP alone, S100B alone, NFL alone, and amyloid PET SUVr in pre-symptomatic AD/PD participants, THEN NVPS will demonstrate stat | NVPS AUC significantly exceeds AUC of best single marker and amyloid PET | — no observation — | pending | 0.55 |
🔮 Falsifiable Predictions (2)
pendingconf 55%
IF NVPS composite score is directly compared head-to-head against plasma GFAP alone, S100B alone, NFL alone, and amyloid PET SUVr in pre-symptomatic AD/PD participants, THEN NVPS will demonstrate statistically significantly higher AUC (DeLong test p<0.05) than the best individual biomarker and amylo
Predicted outcome: NVPS AUC significantly exceeds AUC of best single marker and amyloid PET
Falsification: NVPS AUC ≤ AUC of any individual plasma marker (GFAP, S100B, NFL) or amyloid PET SUVr, or no significant difference (DeLong p≥0.05) between NVPS and best performing comparator
pendingconf 45%
IF the LASSO-optimized NVPS composite panel (plasma GFAP, S100B, NFL, soluble PDGFR-β, claudin-5 fragments) is applied to a pre-symptomatic AD/PD cohort at baseline, THEN the AUC for predicting conversion to symptomatic disease within 5 years will exceed 0.90.
Predicted outcome: AUC >0.90 for NVPS panel in pre-symptomatic AD/PD prediction
Falsification: AUC ≤0.85 for NVPS panel, with 95% CI upper bound below 0.90, using leave-one-out cross-validation on LASSO-optimized weights
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
Public annotations (0)Annotate on Hypothes.is →
No public annotations yet.