Transient Aβ exposure induces dendritic tau missorting that then converts into a locally self-propagating tau oligomer/seeding program. After verified Aβ clearance, continued degeneration is driven by tau seed formation, templated misfolding, and trans-synaptic spread rather than by ongoing amyloid signaling.
Curated pathway from expert analysis
flowchart TD
A["MAPT<br/>Primary Target"]
B["Biological Process 1<br/>Mechanistic Step A"]
C["Biological Process 2<br/>Mechanistic Step B"]
D["Output Phenotype<br/>Disease Effect"]
A --> B
B --> C
C --> D
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D 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.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF APP/PS1dE9 mice receive anti-tau antibody (HJ8.5, 10mg/kg, i.p.) or tau siRNA delivered via AAV9-CamKIIa-eGFP throughout the 30-day period following transient intracerebroventricular Aβ infusion (c | Equivalent neurodegeneration (CA1 neuronal density ≤60% of baseline) and equivalent spatial memory deficits (Barnes maze latency ≥45 sec) in anti-tau/knockdown | — no observation — | pending | 0.58 |
| IF primary cortical neurons are exposed to 1 μM Aβ42 oligomers for 48 hours followed by complete washout and verified Aβ clearance (by ELISA), THEN neuronal lysates collected 14 days post-clearance wi | Increased tau seeding activity (≥2-fold FRET signal) in neuronal lysates at day 14 post-Aβ washout | — no observation — | pending | 0.65 |