Polygenic hazard scores in preclinical Alzheimer disease

Ann Neurol. 2017 Sep;82(3):484-488. doi: 10.1002/ana.25029.


Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484-488.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Multifactorial Inheritance*
  • Neuropsychological Tests
  • Risk Assessment
  • Risk Factors


  • Apolipoprotein E4