Microglial TREM2 Activation to Enhance Synaptic Pruning Regulation
Curated pathway from expert analysis
flowchart TD
A["Amyloid-beta Plaques<br/>Phospholipid Ligands"]
B["TREM2 Receptor<br/>Ligand Binding"]
C["TYROBP/DAP12<br/>ITAM Phosphorylation"]
D["SYK Kinase<br/>Activation"]
E["PLCG2<br/>IP3 + DAG Generation"]
F["Ca2+ Release<br/>Cytoskeletal Remodeling"]
G["Microglial Phagocytosis<br/>Plaque Compaction"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MICROGLIAL yet. Search RCSB →
Median TPM across 13 brain regions for Microglial TREM2 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 Microglial TREM2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we administer a selective TREM2 agonist (anti-TREM2 agonistic antibody at 10mg/kg, weekly ip) to 6-month-old 5xFAD mice for 8 weeks, THEN we will observe a significant reduction in cortical synapti | ≥20% reduction in excitatory synapse density (PSD-95/vGLUT1 puncta) in cortical layer 5 neurons in the agonist-treated group versus vehicle controls | — no observation — | pending | 0.65 |
| IF we perform longitudinal in vivo two-photon microscopy to monitor dendritic spine turnover in Trem2^R47H knock-in mice crossed with Thy1-YFP reporters following a 4-week regimen of TREM2-activating | Spine elimination rate increases to ≥0.05eliminations/hour with unchanged spine formation rate (<0.05/hour), yielding net spine density reduction of 15-25% | — no observation — | pending | 0.58 |