p-tau231 reflects earlier amyloid-driven changes in entorhinal cortex while p-tau217 reflects downstream neuronal involvement. The combination captures the full spectrum of amyloid-to-tau propagation resolution. However, the composite algorithm is not operationally defined, weighting schemes are unspecified, and temporal window evidence from natural disease course may not transfer to treatment kinetics. Addition of p-tau231 may increase assay complexity without proportional predictive gain.
Curated pathway from expert analysis
flowchart TD
A["APP Full Length<br/>Membrane Protein"]
B["BACE1 Beta-Secretase<br/>Cleavage at beta-site"]
C["sAPPbeta + CTFbeta<br/>C-terminal Fragment"]
D["Gamma-Secretase Complex<br/>PSEN1/PSEN2"]
E["Abeta42 Peptide<br/>Amyloidogenic Fragment"]
F["Abeta Oligomers<br/>Toxic Aggregates"]
G["Amyloid Plaques<br/>Extracellular Deposits"]
H["ADAM10 Alpha-Secretase<br/>Non-amyloidogenic Path"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
A --> H
H -.->|"competes with BACE1"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H 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 - Multi-biomarker diagnostic.
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 p-tau231 normalizes before p-tau217 in participants who stop anti-amyloid treatment due to biomarker normalization, THEN the p-tau231 normalization will occur within 3 months of treatment ce | Mean p-tau231 return to baseline/normal levels by month 21 post-treatment cessation; mean p-tau217 return to baseline by month 27 or later | — no observation — | pending | 0.28 |
| IF p-tau231 is added to a p-tau217-only biomarker panel in a randomized controlled trial of anti-amyloid therapy, THEN the composite panel will achieve ≥15% higher specificity (90% vs 75%) for determi | Specificity for treatment cessation determination ≥90% with dual-marker algorithm vs 75% with p-tau217 alone | — no observation — | pending | 0.35 |