A lower effective dose may exist in a sleep-fragmented subgroup if the beneficial mechanism is indirect, via improved slow-wave sleep rather than direct ISR rescue. This is clinically feasible and testable, but current support is stronger for symptomatic sleep benefit than for true disease modification.
Curated pathway from expert analysis
flowchart TD
A["CSF Arterial Inflow<br/>Periarterial Space"]
B["AQP4 on Astrocyte Endfeet<br/>Perivascular Polarization"]
C["Glymphatic Flow<br/>ISF Convective Clearance"]
D["Abeta/Tau Efflux<br/>Perivenous Drainage"]
E["Lymphatic Outflow<br/>Cervical Lymph Nodes"]
F["AQP4 Mislocalization<br/>in AD/Aging"]
G["Reduced ISF Clearance<br/>Aggregate Accumulation"]
A --> B
B --> C
C --> D
D --> E
F -.->|"impairs"| C
F --> G
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#1b5e20,stroke:#81c784,color:#81c784
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for HTR2A; yet. Search RCSB →
Median TPM across 13 brain regions for HTR2A; HRH1; AQP4 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 HTR2A; HRH1; AQP4.
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 trazodone 50-100mg nightly is administered to Alzheimer's disease patients with PSG-confirmed marked slow-wave sleep deficiency (NREM stage 3 < 10% of total sleep time), THEN their slow-wave sleep | Mean NREM stage 3 percentage increases from baseline <10% to ≥15% in the SWS-deficient group | — no observation — | pending | 0.35 |
| IF the dose-response relationship for sleep improvement is subgroup-dependent, THEN Alzheimer's disease patients with marked SWS deficiency (<10% NREM3 at baseline) will show clinically meaningful imp | PSQI reduction ≥3 points in ≥60% of SWS-deficient patients versus <30% of non-deficient patients at 50-100mg trazodone | — no observation — | pending | 0.30 |