A specific threshold represents the point at which amyloid-driven tau pathology has been reduced below the threshold required to sustain neurodegeneration. However, the threshold is operationally undefined—the <0.15 pg/mL value lacks prospective validation and is likely derived from cross-sectional amyloid status cutoffs, not treatment cessation studies. The proposed pragmatic trial to validate this threshold has never been conducted and carries significant ethical and investment risk.
Curated pathway from expert analysis
flowchart TD
A["Testosterone/ANDROGEN RECEPTOR Axis<br/>Neuronal Androgen Binding"]
B["AR Nuclear Translocation<br/>Coactivator Recruitment and Hormonal Ligand"]
C["TM4SF5 and CD82 Expression<br/>Senescent Cell Surface Marker Induction"]
D["Senolytic Target Engagement<br/>p53-Dependent Apoptosis in SASP Cells"]
E["Inflammatory Niche Remodeling<br/>SASP Factor Clearance"]
F["Neurodegenerative Niche Improvement<br/>Reduced Inflammatory Tone"]
A --> B
B --> C
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:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for NA 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 NA - Companion diagnostic target.
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 patients with early Alzheimer's disease who cease anti-amyloid antibody therapy are stratified by baseline CSF p-tau217 (<0.15 pg/mL vs ≥0.15 pg/mL) and followed prospectively for 24 months post-ce | Stratified clinical progression rate difference of ≥0.5 CDR-SB points favoring the <0.15 pg/mL group at 24 months post-cessation | — no observation — | pending | 0.25 |
| IF ROC analysis is performed on CSF p-tau217 values from a treatment cessation cohort to empirically identify the optimal threshold for predicting durable clinical benefit (CDR-SB stability at 18-24 m | Empirically derived optimal threshold deviating ≥30% from 0.15 pg/mL | — no observation — | pending | 0.15 |