Curated pathway from expert analysis
flowchart TD
A["MAPT/Tau Protein<br/>Microtubule Stabilizer"]
B["CDK5/GSK3B Activation<br/>Kinase Dysregulation"]
C["Tau Hyperphosphorylation<br/>Ser396/Thr231/Ser202"]
D["Tau Detachment<br/>Microtubule Destabilized"]
E["Tau Oligomers<br/>Paired Helical Filaments"]
F["Neurofibrillary Tangles<br/>Intraneuronal Inclusions"]
G["Axonal Transport Failure<br/>Synaptic Dysfunction"]
H["Neurodegeneration<br/>Tauopathy Spread"]
A --> B
B --> C
C --> D
D --> E
E --> F
D --> G
G --> H
F --> H
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style C fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for MAPT 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 MAPT.
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 we enroll 120 early-stage Alzheimer's disease subjects (CDR 0.5, amyloid positive by PET) and randomize to 6 months of sleep optimization intervention (auto-CPAP for AHI>15 + sleep hygiene counseli | ≥25% decrease in CSF p-tau181 from baseline in intervention arm; ≥20% lower mean CSF p-tau181 in intervention vs control arm at 6 months | — no observation — | pending | 0.65 |
| IF we recruit 180 amnestic MCI and early AD subjects (CDR 0.5–1.0), stratify them into APOE4 carriers (n=60), APOE4 non-carriers with high sleep fragmentation (ESS >10 or PSG AHI 15–30, n=60), and APO | ≥50% larger PVS volume in APOE4 carriers vs normal-sleep non-carriers; ≥35% higher CSF p-tau181 in APOE4 carriers; APOE4 explains ≥15% of PVS variance | — no observation — | pending | 0.55 |