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Integrative Analysis of Amyloid Imaging and Genetics Reveals Subtypes of Alzheimer Progression in Early Stage

  • Bing He,
  • Neel Sangani,
  • Ruiming Wu,
  • Pradeep Varathan,
  • Alice Patania,
  • Shannon L. Risacher,
  • Kwangsik Nho,
  • Liana G. Apostolova,
  • Andrew J. Saykin,
  • Li Shen,
  • Jingwen Yan

摘要

Alzheimer’s disease (AD) progresses along a continuum and begins many years before symptom onset. Amyloid beta and neurofibrillary tangles are two AD hallmarks that precede changes in cognitive performance and have been utilized in the current framework for classification and staging of AD patients. This framework, however, relies on the dichotomous classification of individual biomarkers (e.g., amyloid positive or negative) and therefore cannot capture the full spectrum of AD progression. In this study, we propose a multi-factorial pseudotime approach that integrates heterogeneous genotype and amyloid imaging data for continuous staging of AD. Our new staging score demonstrated strong capability in differentiating early-stage subjects with distinct progression rates, suggesting its potential in supplementing existing diagnostic framework for early risk stratification.