AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Positive Individuals Never Develop Dementia

SUMMARY

# AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Positive Individuals Never Develop Dementia ## Background and Rationale This groundbreaking study addresses one of Alzheimer's disease research's most compelling mysteries: why some individuals can harbor significant amyloid pathology yet maintain normal cognitive function throughout their lives. This phenomenon, termed 'amyloid resilience,' represents a natural experiment that could unlock protective mechanisms applicable to therapeutic

METHODOLOGY NOTES

**Phase 1: Participant Recruitment and Screening (Months 1-6)** • Recruit 300 amyloid-positive individuals aged 65+ through memory clinics and research registries • Screen using PET amyloid imaging (Pittsburgh Compound B or florbetapir) with standardized uptake value ratio (SUVR) ≥1.11 • Administer comprehensive cognitive battery: MMSE, MoCA, CDR, and neuropsychological assessment • Classify participants into resilient (n=150, cognitively normal despite amyloid+) and vulnerable (n=150, MCI/dementia with amyloid+) groups • Obtain informed consent and collect demographic data, medical history, and APOE genotyping **Phase 2: Baseline Multimodal Assessment (Months 7-12)** • Conduct structural MRI with volumetric analysis of hippocampus, entorhinal cortex, and cortical thickness measurements • Perform FDG-PET imaging to assess glucose metabolism in AD-vulnerable regions • Collect cerebrospinal fluid via lumbar puncture for biomarker analysis: Aβ42, total tau, p-tau181, neurofilament light