SUMMARY
# Senolytic Therapy (D+Q) Phase IIa Trial in Early Alzheimer's Disease
## Background and Rationale
This Phase IIa clinical trial evaluates the therapeutic potential of senolytic therapy using dasatinib plus quercetin (D+Q) in early Alzheimer's disease patients, targeting the senescence-associated secretory phenotype (SASP) that contributes to neuroinflammation and cognitive decline. Cellular senescence accumulates in the aging brain and is accelerated in AD, with senescent cells secreting pro-in
METHODOLOGY NOTES
**Phase 1: Screening and Baseline Assessment (Weeks -4 to 0)**
• Screen 200 potential participants aged 60-85 with mild cognitive impairment or early AD (CDR 0.5-1.0)
• Confirm amyloid positivity via PET imaging (Centiloid >20) or CSF Aβ42/40 ratio <0.067
• Obtain comprehensive neuropsychological battery (ADAS-Cog, MMSE, CDR-SB, FAQ)
• Collect baseline blood biomarkers: p16INK4a, p21, IL-6, TNF-α, SASP factors
• Perform baseline brain MRI with volumetric analysis and DTI sequences
• Lumbar puncture for CSF collection: Aβ40, Aβ42, tau, p-tau181, neurofilament light
• Randomize 120 eligible participants 1:1 to D+Q vs placebo arms (n=60 each)
**Phase 2: Treatment Period (Weeks 1-24)**
• Administer dasatinib 100mg + quercetin 1000mg orally for 2 consecutive days every 4 weeks (6 cycles total)
• Placebo group receives matched capsules on same schedule
• Safety monitoring every 2 weeks: CBC, comprehensive metabolic panel, liver enzymes
• Cognitive assessments at weeks 4, 8, 12, 18, and 24
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