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

dc.contributor.authorReiman, Eric M.
dc.contributor.authorArboleda-Velasquez, Joseph F.
dc.contributor.authorQuiroz, Yakeel T.
dc.contributor.authorHuentelman, Matthew J.
dc.contributor.authorBeach, Thomas G.
dc.contributor.authorCaselli, Richard J.
dc.contributor.authorChen, Yinghua
dc.contributor.authorSu, Yi
dc.contributor.authorMyers, Amanda J.
dc.contributor.authorHardy, John
dc.contributor.authorVonsattel, Jean Paul
dc.contributor.authorYounkin, Steven G.
dc.contributor.authorBennett, David A.
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorLarson, Eric B.
dc.contributor.authorCrane, Paul K.
dc.contributor.authorKeene, C. Dirk
dc.contributor.authorKamboh, M. Ilyas
dc.contributor.authorKofler, Julia K.
dc.contributor.authorDuque, Linda
dc.contributor.authorGilbert, John R.
dc.contributor.authorGwirtsman, Harry E.
dc.contributor.authorBuxbaum, Joseph D.
dc.contributor.authorDickson, Dennis W.
dc.contributor.authorFrosch, Matthew P.
dc.contributor.authorGhetti, Bernardino F.
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorWang, Li-San
dc.contributor.authorHyman, Bradley T.
dc.contributor.authorKukull, Walter A.
dc.contributor.authorForoud, Tatiana
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorMayeux, Richard P.
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorSchneider, Julie A.
dc.contributor.authorTrojanowski, John Q.
dc.contributor.authorFarrer, Lindsay A.
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorBeecham, Gary W.
dc.contributor.authorMontine, Thomas J.
dc.contributor.authorJun, Gyungah R.
dc.contributor.authorAlzheimer’s Disease Genetics Consortium
dc.contributor.departmentPathology and Laboratory Medicine, School of Medicineen_US
dc.description.abstractEach 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationReiman, E. M., Arboleda-Velasquez, J. F., Quiroz, Y. T., Huentelman, M. J., Beach, T. G., Caselli, R. J., Chen, Y., Su, Y., Myers, A. J., Hardy, J., Paul Vonsattel, J., Younkin, S. G., Bennett, D. A., De Jager, P. L., Larson, E. B., Crane, P. K., Keene, C. D., Kamboh, M. I., Kofler, J. K., Duque, L., … Alzheimer’s Disease Genetics Consortium (2020). Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nature communications, 11(1), 667. https://doi.org/10.1038/s41467-019-14279-8en_US
dc.publisherNature Researchen_US
dc.relation.journalNature Communicationsen_US
dc.rightsAttribution 4.0 International*
dc.subjectAlzheimer's diseaseen_US
dc.subjectGenetics researchen_US
dc.titleExceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological studyen_US
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