HBOT promotes pericyte survival via PDGF-BB/PDGFR-β signaling and upregulates claudin-5 transcription through HIF-2α to repair BBB breakdown in AD. However, tight-junction upregulation is not equivalent to restored BBB function; endothelial transcytosis, basement membrane changes, and astrocytic endfeet dysfunction also contribute to BBB failure. The 90-day duration claim is clinically impractical.
Curated pathway from expert analysis
flowchart TD
A["HBOT 1.5 ATA<br/>90 days"]
B["HIF-2a<br/>Upregulation"]
C["Claudin-5<br/>Transcription Increase"]
D["Pericyte<br/>Survival via PDGF-BB"]
E["Tight Junction<br/>Repair"]
F["BBB Integrity<br/>Restoration"]
A --> B
B --> C
A --> D
D --> C
C --> E
E --> F
style A fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7
style B fill:#004d40,stroke:#80cbc4,color:#80cbc4
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for CLDN5 yet. Search RCSB →
Median TPM across 13 brain regions for CLDN5 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 CLDN5.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF 5xFAD transgenic mice undergo HBOT at 1.5 ATA for 90 days, THEN pericyte coverage of cerebral microvessels will increase by at least 30% and PDGFR-β expression will upregulate, restoring BBB leakag | Pericyte coverage (NG2+/PDGFR-β+ cells per vessel length) increases by 30%+ and BBB permeability (Evans Blue or sodium fluorescein extravasation) decreases to w | — no observation — | pending | 0.55 |
| IF patients with confirmed Alzheimer's disease receive HBOT at 1.5 ATA for 90 consecutive days (60 sessions), THEN cerebrospinal fluid claudin-5 protein levels will increase by at least 25% relative t | CSF claudin-5 concentration increases by 25-40% post-intervention compared to pre-HBOT baseline, detectable via ELISA | — no observation — | pending | 0.45 |