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Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer’s disease

Author

Listed:
  • Manish D Paranjpe
  • Mark Chaffin
  • Sohail Zahid
  • Scott Ritchie
  • Jerome I Rotter
  • Stephen S Rich
  • Robert Gerszten
  • Xiuqing Guo
  • Susan Heckbert
  • Russ Tracy
  • John Danesh
  • Eric S Lander
  • Michael Inouye
  • Sekar Kathiresan
  • Adam S Butterworth
  • Amit V Khera

Abstract

For Alzheimer’s disease–a leading cause of dementia and global morbidity–improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer’s disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer’s disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p

Suggested Citation

  • Manish D Paranjpe & Mark Chaffin & Sohail Zahid & Scott Ritchie & Jerome I Rotter & Stephen S Rich & Robert Gerszten & Xiuqing Guo & Susan Heckbert & Russ Tracy & John Danesh & Eric S Lander & Michael, 2022. "Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer’s disease," PLOS Genetics, Public Library of Science, vol. 18(9), pages 1-20, September.
    • Handle: RePEc:plo:pgen00:1010294
    DOI: 10.1371/journal.pgen.1010294
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