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Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study

Author

Listed:
  • Eric M. Reiman

    (Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium
    University of Arizona
    Arizona State University
    Translational Genomics Research Institute and Arizona Alzheimer’s Consortium)

  • Joseph F. Arboleda-Velasquez

    (Schepens Eye Research Institute of Mass Eye and Ear and the Department of Ophthalmology at Harvard Medical School)

  • Yakeel T. Quiroz

    (Massachusetts General Hospital and Harvard Medical School)

  • Matthew J. Huentelman

    (Translational Genomics Research Institute and Arizona Alzheimer’s Consortium)

  • Thomas G. Beach

    (Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium)

  • Richard J. Caselli

    (Mayo Clinic)

  • Yinghua Chen

    (Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium)

  • Yi Su

    (Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium)

  • Amanda J. Myers

    (University of Miami Miller School of Medicine)

  • John Hardy

    (Institute of Neurology)

  • Jean Paul Vonsattel

    (New York-Presbyterian Hospital at Columbia University Medical Center)

  • Steven G. Younkin

    (Mayo Clinic)

  • David A. Bennett

    (Rush University Medical Center)

  • Philip L. Jager

    (Columbia University Medical Center)

  • Eric B. Larson

    (Kaiser Permanente Washington Health Research Institute)

  • Paul K. Crane

    (University of Washington)

  • C. Dirk Keene

    (University of Washington)

  • M. Ilyas Kamboh

    (University of Pittsburgh)

  • Julia K. Kofler

    (University of Pittsburgh)

  • Linda Duque

    (University of Miami)

  • John R. Gilbert

    (University of Miami)

  • Harry E. Gwirtsman

    (Vanderbilt University)

  • Joseph D. Buxbaum

    (Mount Sinai School of Medicine)

  • Dennis W. Dickson

    (Mayo Clinic)

  • Matthew P. Frosch

    (Massachusetts General Hospital)

  • Bernardino F. Ghetti

    (Indiana University)

  • Kathryn L. Lunetta

    (Boston University School of Public Health)

  • Li-San Wang

    (University of Pennsylvania Perelman School of Medicine)

  • Bradley T. Hyman

    (Massachusetts General Hospital and Harvard Medical School)

  • Walter A. Kukull

    (University of Washington)

  • Tatiana Foroud

    (Indiana University)

  • Jonathan L. Haines

    (Case Western Reserve University)

  • Richard P. Mayeux

    (Columbia University)

  • Margaret A. Pericak-Vance

    (University of Miami)

  • Julie A. Schneider

    (Rush University Medical Center)

  • John Q. Trojanowski

    (University of Pennsylvania Perelman School of Medicine)

  • Lindsay A. Farrer

    (Boston University School of Public Health
    Boston University School of Medicine
    Boston University School of Medicine
    Boston University School of Public Health)

  • Gerard D. Schellenberg

    (University of Pennsylvania Perelman School of Medicine)

  • Gary W. Beecham

    (University of Miami)

  • Thomas J. Montine

    (Stanford University)

  • Gyungah R. Jun

    (Boston University School of Medicine)

Abstract

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with a low Alzheimer’s dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of the disease.

Suggested Citation

  • Eric M. Reiman & Joseph F. Arboleda-Velasquez & Yakeel T. Quiroz & Matthew J. Huentelman & Thomas G. Beach & Richard J. Caselli & Yinghua Chen & Yi Su & Amanda J. Myers & John Hardy & Jean Paul Vonsat, 2020. "Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14279-8
    DOI: 10.1038/s41467-019-14279-8
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