A longitudinal biomarker panel centered on plasma LPS-binding protein can distinguish harmful mechanisms from protective adaptation. The decisive experiment is to measure plasma LPS-binding protein before and after TLR4 antagonism in stratified models.
Curated pathway from expert analysis
flowchart TD
A["Gut Dysbiosis<br/>SCFA-Producing Bacteria Loss"]
B["Intestinal Permeability<br/>Leaky Gut Endotoxemia"]
C["LPS Translocation<br/>Portal and Systemic Circulation"]
D["TLR4 Activation<br/>MD-2 Coreceptor Complex"]
E["MyD88 Signaling<br/>NF-kappaB and MAPK Cascade"]
F["Peripheral Cytokine Storm<br/>IL-1beta and TNF Secretion"]
G["Microglial Priming<br/>Brain Resident Immune Activation"]
H["Neurodegeneration<br/>Synapse Loss and Tau Pathology"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo curated PDB or AlphaFold mapping for PLASMA 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 plasma LPS-binding protein.
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 plasma LPS-binding protein separates causal dysbiosis from compensation, THEN baseline LBP in high-dysbiosis participants will predict >=20% faster rise in plasma GFAP or NfL over 18 months. | Top-tertile LBP among dysbiotic participants predicts >=20% higher annual GFAP/NfL slope than bottom tertile. | — no observation — | pending | 0.58 |
| IF LBP marks harmful SCFA-depletion states, THEN restoring butyrate-producing taxa will lower plasma LBP by >=15% and microglial activation PET signal by >=10% within 12 weeks. | Butyrate-restoration intervention reduces LBP >=15% and TSPO-PET or equivalent neuroinflammation marker >=10%. | — no observation — | pending | 0.50 |