📋 Research Plan
alzheimerCDK5$1,200,00018 monthsN = 60
Assay
Protocol: Intermittent oral ABT-263 (100mg/m²) + dasatinib (20mg/m²) on Days 1-3 every 28 days.
Cohort: Early AD (MMSE 20-26), N=60, 1:1 randomization, 12-month treatment.
Controls: Age/sex-matched placebo, 5xFAD senolytic-non-responsive model.
Biomarkers: (1) CSF p-tau181 and t-tau (primary), (2) SUVr tau PET (secondary), (3) senescence markers (p16INK4a in peripheral blood mononuclear cells), (4) cognition (ADAS-Cog13).
Power: Pilot study, 80% power to detect 30% reduction in p-tau181 at α=0.10 (exploratory).
Primary endpoint
12-month change in CSF p-tau181 concentration from baseline
Kill criteria
- No reduction in peripheral senescence markers (p16INK4a)
- CSF p-tau181 not reduced vs placebo
- TAU PET uptake increased > 10% in treatment arm
- Grade 3+ thrombocytopenia in > 15% of subjects
Power: {'test': 'two-sample t-test', 'alpha': 0.1, 'power': 0.8, 'effect_size': 0.55, 'expected_dropout': 0.15}