SUMMARY
# Proposed experiment from debate on Synaptic pruning by microglia in early AD
## Background and Rationale
This study tests whether complement-mediated synaptic pruning can be therapeutically modulated using decoy molecules in Alzheimer's disease mouse models. The complement system, particularly C1q, has emerged as a key mediator of pathological synapse loss in AD through tagging synapses for microglial elimination. This falsification experiment uses C1q-sufficient versus C1q-deficient AD transg
METHODOLOGY NOTES
**Phase 1: Animal Preparation and Randomization (Weeks 1-2)**
• Obtain 120 APP/PS1 transgenic mice (8-10 weeks old) and 60 C1q knockout (C1qa-/-) mice crossed with APP/PS1
• Randomize into 6 groups (n=30 each): APP/PS1+vehicle, APP/PS1+decoy, APP/PS1+scrambled decoy, C1qa-/-APP/PS1+vehicle, C1qa-/-APP/PS1+decoy, C1qa-/-APP/PS1+scrambled decoy
• Baseline cognitive testing using Morris water maze and novel object recognition
• Collect baseline blood samples for immune profiling
**Phase 2: Decoy Molecule Treatment (Weeks 3-14)**
• Administer C1q decoy molecules (10 mg/kg) or scrambled control via osmotic pumps replaced bi-weekly
• Weekly body weight monitoring and general health assessment
• Bi-weekly blood collection for C1q levels and immune markers
**Phase 3: Systemic Immune Function Testing (Weeks 8-10)**
• Bacterial clearance assay: Inject E. coli (10^6 CFU) i.p., measure bacterial load in blood/organs at 4, 8, 24h
• Autoantibody assessment: Weekly serum collection for anti-nuclear