EXCEPTIONALLY LOW LIKELIHOOD OF ALZHEIMER’S DEMENTIA IN APOE2 HOMOZYGOTES

Eric M Reiman, et al.

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Nov 06, 2019
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Received Date: 1st October 19

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 Vonsattel, Steven G. Younkin,  David A. Bennett,  Philip L. De Jager, Eric B. Larson,  Paul K. Crane, C. Dirk Keene,  M. Ilyas Kamboh, Julia K. Kofler, Linda Duque, John R. Gilbert, Harry E. Gwirtsman,  Joseph D. Buxbaum,  Dennis W. Dickson, Matthew P. Frosch, Bernardino Ghetti,  Kathryn L. Lunetta,  Li-San Wang, Bradley T. Hyman, Walter A. Kukull,  Tatiana Foroud, Jonathan L. Haines,  Richard P. Mayeux, Margaret A. Pericak-Vance, Julie A. Schneider, John Q. Trojanowski,  Lindsay A. Farrer,  Gerard D. Schellenberg, Gary W. Beecham, Thomas J. Montine, Gyungah R. Jun, Alzheimers Disease Genetics Consortium

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, such that APOE4 homozygotes have a particularly high risk. 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 exceptionally low Alzheimer’s dementia odds ratios compared to APOE2/3, 3/3 and 4/4, 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 this terrible disease.

Read in full at medRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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