TREM2 KO amyloid pathology study

Expected Outcomes

Primary Outcomes

Expected Outcomes

Primary Outcomes

Secondary Outcomes

• TREM2 KO mice may show increased soluble Aβ42/Aβ40 ratio in brain lysates
• Reduced microglial clustering around plaques in TREM2-/- (assessed by IBA1 co-staining)
• No gross phenotypic differences between groups expected

Negative/Null Result Interpretation

• If no difference observed, may indicate TREM2 role is pathway-specific or age-dependent
• Null result at 6 months should prompt re-analysis at 9+ months

Success Criteria

Primary

• [ ] ≥30% increase in cortical Aβ % area coverage in 5xFAD/TREM2-/- vs 5xFAD/TREM2+/+ (p < 0.05)
• [ ] ≥30% increase in hippocampal Aβ % area coverage (p < 0.05)
• [ ] Effect reproduces in both 6-month and 9-month cohorts

Secondary

• [ ] Thioflavin-S+ plaque density quantified in both groups
• [ ] IBA1 microglial density around plaques quantified
• [ ] All controls pass QC (positive shows >10% area, negative shows <0.5% area)

Success Criteria

Primary

• [ ] ≥30% increase in cortical Aβ % area coverage in 5xFAD/TREM2-/- vs 5xFAD/TREM2+/+ (p < 0.05)
• [ ] ≥30% increase in hippocampal Aβ % area coverage (p < 0.05)
• [ ] Effect reproduces in both 6-month and 9-month cohorts

Secondary

• [ ] Thioflavin-S+ plaque density quantified in both groups
• [ ] IBA1 microglial density around plaques quantified
• [ ] All controls pass QC (positive shows >10% area, negative shows <0.5% area)

Technical Quality Gates

• [ ] ≥8/10 animals per group yield analyzable histology sections
• [ ] Genotyping confirmed for 100% of animals included in analysis
• [ ] Antibody staining variability (CV) < 15% across sections from same animal
• [ ] Blinded analysis performed (analyst unaware of genotype during quantification)