📋 Research Plan
alzheimerACE$890,00012 monthsN = 60
Assay
Protocol: AAV9-mediated ACE overexpression under CD68 promoter (microglia-specific).
Reagents: AAV9-hACE2 vector (1×10^12 vg/mL), control AAV9-GFP.
Animal model: 5xFAD mice, 3 months old, N=60 (30 treatment, 30 control).
Outcome measures: (1) Aβ plaque burden (Thioflavin S + 6E10 IHC), (2) soluble Aβ40/42 (ELISA), (3) microglial coverage (Iba1+), (4) inflammatory cytokines (IL-1β, TNF-α, IL-6 by qPCR), (5) Morris water maze at 9 months.
Power calculation: Two-group comparison, effect size 0.55 (based on prior ACE expression data), α=0.05, power=0.80 → n=26/group.
Primary endpoint
Aβ plaque burden reduction (%) at 6 months post-treatment
Kill criteria
- Aβ plaque reduction < 20% vs control
- No change in microglial Aβ phagocytosis rate (in vitro assay)
- Increased neuroinflammation markers (IL-1β > 2x baseline)
- Off-target integration > 1% by WGS
Power: {'test': 'two-sample t-test', 'alpha': 0.05, 'power': 0.8, 'effect_size': 0.55, 'expected_dropout': 0.1}