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

dc.contributor.authorGwirtsman, Harry E.
dc.date.accessioned2020-10-07T18:46:37Z
dc.date.available2020-10-07T18:46:37Z
dc.date.issued2020-02-03
dc.identifier.citationReiman, E.M., Arboleda-Velasquez, J.F., Quiroz, Y.T. et al. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun 11, 667 (2020). https://doi.org/10.1038/s41467-019-14279-8en_US
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1803/16195
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.nature.com/articles/s41467-019-14279-8#article-infoen_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.description.sponsorshipThis study was supported by the NIA Grants RF1AG057519, P30AG10161, R01AG15819, R01AG17917, R01AG031581, and P30AG19610 for the Arizona Alzheimer's Disease Core Center; Arizona Department of Health Services contract 211002 for the Arizona Alzheimer's Research Center; Arizona Biomedical Research Commission contracts 4001 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium; and the Michael J. Fox Foundation for Parkinson's Research. The Alzheimer's Disease Genetics Consortium supported the collection of samples used in this study through NIA U01AG032984 and RC2AG036528. Data for this study were prepared, archived, and distributed by the NIA Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania and funded by NIA Grant U24AG041689. This work was also supported by NIA Grants R01AG048927, R01AG032990, RFAG051504, U01AG046139, AG030653, AG041718, AG005133, P50AG005136 (UW ADRC NP Core) and U01AG006781 (ACT), and the Nancy and Buster Alvord Endowment (CDK), as well as by National Institute of Neurological Disorders and Stroke (NINDS) Grant R01NS080820 (to NET). The Brain and Body Donation Program at Sun Health Research Institute (Sun City, AZ, USA) is supported by NINDS Grant U24NS072026 for the National Brain and Tissue Resource for Parkinson's Disease and Related disorders. National Institute of Neurological Disorders and Stroke NINDS Grants (UG3NS115605 and RF1NS110048).en_US
dc.language.isoen_USen_US
dc.publisherNature Communicationsen_US
dc.rightsOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://www.nature.com/articles/s41467-019-14279-8#rightslink
dc.titleExceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological studyen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-019-14279-8


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