Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study-Reference-Cited by-同舟云学术

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

Published:2020-02-03 Issue:1 Volume:11 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Reiman Eric M.^ORCID, ,Arboleda-Velasquez Joseph F.^ORCID,Quiroz Yakeel T.,Huentelman Matthew J.,Beach Thomas G.,Caselli Richard J.,Chen Yinghua,Su Yi,Myers Amanda J.,Hardy John,Paul Vonsattel Jean,Younkin Steven G.,Bennett David A.,De Jager Philip L.,Larson Eric B.,Crane Paul K.,Keene C. Dirk,Kamboh M. Ilyas,Kofler Julia K.,Duque Linda,Gilbert John R.,Gwirtsman Harry E.,Buxbaum Joseph D.,Dickson Dennis W.^ORCID,Frosch Matthew P.,Ghetti Bernardino F.^ORCID,Lunetta Kathryn L.^ORCID,Wang Li-San,Hyman Bradley T.^ORCID,Kukull Walter A.,Foroud Tatiana,Haines Jonathan L.^ORCID,Mayeux Richard P.,Pericak-Vance Margaret A.^ORCID,Schneider Julie A.,Trojanowski John Q.^ORCID,Farrer Lindsay A.,Schellenberg Gerard D.,Beecham Gary W.,Montine Thomas J.,Jun Gyungah R.^ORCID

Abstract

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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute on Aging

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-019-14279-8.pdf

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