Curated pathway from expert analysis
flowchart TD
A["APOE4 Isoform<br/>Structural Instability"]
B["Impaired Lipid Loading<br/>Reduced Cholesterol Efflux"]
C["LRP1 Reduced Binding<br/>BBB Clearance Deficit"]
D["Amyloid-beta<br/>Accumulation"]
E["Synaptic Dysfunction<br/>Membrane Disruption"]
F["Neurodegeneration<br/>Cognitive Decline"]
G["APOE3 Comparison<br/>Normal Lipidation"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"protective"| C
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for APOE 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 APOE.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF 10-month-old APOE4/4 knock-in mice receive daily oral LXRβ agonist (GW3965, 10mg/kg) for 5 months, THEN cortical amyloid plaque burden will decrease by ≥40% compared to vehicle-treated APOE4/4 mice | ≥40% reduction in Thioflavin-S+ plaque area fraction in cortex of treated vs. control mice | — no observation — | pending | 0.35 |
| IF human iPSC-derived astrocytes homozygous for APOE4 are treated with an LXRβ-selective agonist (e.g., GSK2033 at 1μM) for 72 hours, THEN conditioned medium APOE4 lipidation will increase by ≥30% rel | ≥30% increase in lipidated APOE4 species (band density ratio) in treatment vs. vehicle condition | — no observation — | pending | 0.45 |