Microglial TREM2 Agonist In Vivo Efficacy

SUMMARY

# Microglial TREM2 Agonist In Vivo Efficacy ## Background and Rationale This validation experiment investigates the therapeutic potential of TREM2 agonistic antibodies in Alzheimer's disease mouse models. TREM2 is a crucial microglial receptor that regulates microglial activation, phagocytosis, and survival, with loss-of-function variants significantly increasing AD risk. The study employs transgenic AD mouse models (such as 5xFAD or APP/PS1) to evaluate whether TREM2 agonistic antibodies can en

METHODOLOGY NOTES

**Phase 1: Animal Preparation and Randomization (Days -7 to 0)** • Obtain 120 APP/PS1 transgenic mice (8-10 months old) and 40 wild-type controls • Acclimate animals for 7 days in controlled environment (12h light/dark cycle, 22°C) • Perform baseline cognitive testing using Morris Water Maze (5 days) • Randomize APP/PS1 mice into 4 groups (n=30 each): vehicle control, low-dose TREM2 agonist (5 mg/kg), medium-dose (15 mg/kg), high-dose (30 mg/kg) • Collect baseline blood samples for biomarker analysis **Phase 2: Treatment Administration (Days 1-56)** • Administer TREM2 agonistic antibodies via intraperitoneal injection twice weekly • Monitor body weight and general health status daily • Perform weekly neurological assessments using standardized scoring system • Collect blood samples at weeks 2, 4, and 6 for pharmacokinetics and inflammatory markers **Phase 3: Cognitive Assessment (Days 50-56)** • Conduct Morris Water Maze testing (acquisition: 4 days, probe trial: day 5) • Perform Nov