Aβ drives tau into dendritic spines, where tau binds Fyn and stabilizes a PSD95-NMDAR-associated excitotoxic scaffold. Once assembled, this complex may persist after Aβ clearance and maintain calcium dysregulation, hyperexcitability, and synaptic degeneration.
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,FYN,DLG4,GRIN2B 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,FYN,DLG4,GRIN2B.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF wild‑type mice receive a single intracerebroventricular injection of Aβ1‑42 oligomers (300 pmol) followed by a 7‑day Aβ‑free period, THEN the amount of Fyn‑tau‑PSD95‑NMDAR complex recovered from sy | 2‑fold increase in co‑immunoprecipitated Fyn/tau/PSD95/GRIN2B and a ≥30 % rise in basal calcium fluorescence (GCaMP6f) in CA1 pyramidal neurons. | — no observation — | pending | 0.65 |
| IF human iPSC‑derived cortical neurons are exposed to 200 nM Aβ1‑42 oligomers for 48 h, THEN after a 96‑h Aβ‑free interval the tau Y18 phosphorylation (Fyn site) co‑localized with PSD95 will stay >1.5 | ≥1.5‑fold increase in PLA puncta for pTau(Y18)–PSD95 and ≥40 % decrease in mEPSC frequency. | — no observation — | pending | 0.60 |