Identification of a TREM2-independent disease-associated microglial (DAM) trajectory in late-stage AD. Single-cell analysis reveals microglial subclusters expressing elevated APOE, CSF1R, and CX3CR1 without TREM2 activation markers, suggesting an alternative activation pathway driving neuroinflammation through C3 upregulation.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
CSF1R["CSF1R"] -->|regulates| neuroinflammation["neuroinflammation"]
CSF1R_1["CSF1R"] -->|regulates| microglial_activation["microglial_activation"]
CSF1R_2["CSF1R"] -->|regulates| Microglial_activation["Microglial activation"]
style CSF1R fill:#ce93d8,stroke:#333,color:#000
style neuroinflammation fill:#4fc3f7,stroke:#333,color:#000
style CSF1R_1 fill:#ce93d8,stroke:#333,color:#000
style microglial_activation fill:#4fc3f7,stroke:#333,color:#000
style CSF1R_2 fill:#ce93d8,stroke:#333,color:#000
style Microglial_activation fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 CSF1R.
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 pharmacologic CSF1R inhibition (PLX3397 or BLZ945, 100mg/kg daily for 4-8 weeks) is administered in a late-stage AD mouse model (5xFAD at 9 months), THEN C3 expression in isolated CD11b+ microglial | ≥50% reduction in microglial C3 mRNA and protein levels following CSF1R blockade in late-stage AD | — no observation — | pending | 0.60 |
| IF TREM2 is genetically knocked out in 5xFAD mice (crossed with Trem2-/-), THEN single-cell RNA sequencing at 9 months will reveal a microglial subcluster expressing elevated APOE, CSF1R, and CX3CR1 ( | Identical DAM subcluster with high APOE, CSF1R, CX3CR1 and low TREM2 activation markers in TREM2 knockout AD mice | — no observation — | pending | 0.55 |