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

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...

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Autores principales: Reiman, Eric M., Arboleda-Velasquez, Joseph F., 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., Frosch, Matthew P., Ghetti, Bernardino F., Lunetta, Kathryn L., Wang, Li-San, Hyman, Bradley T., Kukull, Walter A., Foroud, Tatiana, Haines, Jonathan L., Mayeux, Richard P., Pericak-Vance, Margaret A., Schneider, Julie A., Trojanowski, John Q., Farrer, Lindsay A., Schellenberg, Gerard D., Beecham, Gary W., Montine, Thomas J., Jun, Gyungah R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997393/
https://www.ncbi.nlm.nih.gov/pubmed/32015339
http://dx.doi.org/10.1038/s41467-019-14279-8
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author Reiman, Eric M.
Arboleda-Velasquez, Joseph F.
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.
Frosch, Matthew P.
Ghetti, Bernardino F.
Lunetta, Kathryn L.
Wang, Li-San
Hyman, Bradley T.
Kukull, Walter A.
Foroud, Tatiana
Haines, Jonathan L.
Mayeux, Richard P.
Pericak-Vance, Margaret A.
Schneider, Julie A.
Trojanowski, John Q.
Farrer, Lindsay A.
Schellenberg, Gerard D.
Beecham, Gary W.
Montine, Thomas J.
Jun, Gyungah R.
author_facet Reiman, Eric M.
Arboleda-Velasquez, Joseph F.
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.
Frosch, Matthew P.
Ghetti, Bernardino F.
Lunetta, Kathryn L.
Wang, Li-San
Hyman, Bradley T.
Kukull, Walter A.
Foroud, Tatiana
Haines, Jonathan L.
Mayeux, Richard P.
Pericak-Vance, Margaret A.
Schneider, Julie A.
Trojanowski, John Q.
Farrer, Lindsay A.
Schellenberg, Gerard D.
Beecham, Gary W.
Montine, Thomas J.
Jun, Gyungah R.
author_sort Reiman, Eric M.
collection PubMed
description 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.
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spelling pubmed-69973932020-02-05 Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study Reiman, Eric M. Arboleda-Velasquez, Joseph F. 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. Frosch, Matthew P. Ghetti, Bernardino F. Lunetta, Kathryn L. Wang, Li-San Hyman, Bradley T. Kukull, Walter A. Foroud, Tatiana Haines, Jonathan L. Mayeux, Richard P. Pericak-Vance, Margaret A. Schneider, Julie A. Trojanowski, John Q. Farrer, Lindsay A. Schellenberg, Gerard D. Beecham, Gary W. Montine, Thomas J. Jun, Gyungah R. Nat Commun Article 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. Nature Publishing Group UK 2020-02-03 /pmc/articles/PMC6997393/ /pubmed/32015339 http://dx.doi.org/10.1038/s41467-019-14279-8 Text en © The Author(s) 2020 Open 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/.
spellingShingle Article
Reiman, Eric M.
Arboleda-Velasquez, Joseph F.
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.
Frosch, Matthew P.
Ghetti, Bernardino F.
Lunetta, Kathryn L.
Wang, Li-San
Hyman, Bradley T.
Kukull, Walter A.
Foroud, Tatiana
Haines, Jonathan L.
Mayeux, Richard P.
Pericak-Vance, Margaret A.
Schneider, Julie A.
Trojanowski, John Q.
Farrer, Lindsay A.
Schellenberg, Gerard D.
Beecham, Gary W.
Montine, Thomas J.
Jun, Gyungah R.
Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title_full Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title_fullStr Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title_full_unstemmed Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title_short Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
title_sort exceptionally low likelihood of alzheimer’s dementia in apoe2 homozygotes from a 5,000-person neuropathological study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997393/
https://www.ncbi.nlm.nih.gov/pubmed/32015339
http://dx.doi.org/10.1038/s41467-019-14279-8
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