This hypothesis is biologically plausible and potentially important for circuit-level phenotypes, but current support is stronger for contextual selectivity than for distinct intrinsic C1q biochemical programs at inhibitory versus excitatory terminals. It is more valuable for endpoint design and disease-stage interpretation than as a near-term therapeutic thesis.
Curated pathway from expert analysis
flowchart TD
A["Stressed Synapse<br/>C1q Ligand Exposed"]
B["C1q Deposition<br/>Synaptic Tagging"]
C["C3 Cleavage<br/>C3b Opsonization"]
D["CR3 Recognition<br/>Microglial Receptor"]
E["Synaptic Pruning<br/>Phagocytic Engulfment"]
F["Synapse Loss<br/>Circuit Disruption"]
G["Cognitive Decline<br/>Memory Impairment"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for C1QA,C1QB,C1QC,GAD1,GAD2,SLC6A1,SLC17A7,ITGAM,ITGB2 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 C1QA,C1QB,C1QC,GAD1,GAD2,SLC6A1,SLC17A7,ITGAM,ITGB2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C1q is globally knocked out in mice from birth, THEN excitatory dendritic spine density will increase by >30% relative to wild‑type while inhibitory synapse puncta (GAD1+) remain unchanged at 8 wee | Excitatory spine density will be >30% higher in C1q KO vs WT; GAD1+ puncta will show <5% change. | — no observation — | pending | 0.55 |
| IF C1q is acutely overexpressed in adult mouse visual cortex via AAV for 4 weeks, THEN excitatory synapse density will decrease by >20% while inhibitory synapse density remains unchanged. | Excitatory synaptic markers (VGLUT1) will be reduced >20% and inhibitory markers (GAD1) will show <5% change. | — no observation — | pending | 0.60 |