Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study
| Autor: | 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 F, 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, Yi, Zhao |
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| Přispěvatelé: | Reiman, Eric M [0000-0002-0705-3696], Arboleda-Velasquez, Joseph F [0000-0002-3192-9117], Dickson, Dennis W [0000-0001-7189-7917], Ghetti, Bernardino F [0000-0002-1842-8019], Lunetta, Kathryn L [0000-0002-9268-810X], Hyman, Bradley T [0000-0002-7959-9401], Haines, Jonathan L [0000-0002-4351-4728], Pericak-Vance, Margaret A [0000-0001-7283-8804], Trojanowski, John Q [0000-0002-9239-8794], Jun, Gyungah R [0000-0002-3230-8697], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Apolipoprotein E Male Aging Apolipoprotein E2 Apolipoprotein E4 Apolipoprotein E3 General Physics and Astronomy Disease Neurodegenerative Alzheimer's Disease 0302 clinical medicine Genotype Genetics research 80 and over 2.1 Biological and endogenous factors Aetiology lcsh:Science Neuropathology Aged 80 and over Multidisciplinary Homozygote Brain Middle Aged Alzheimer's disease Neurological Female medicine.medical_specialty Science Lower risk General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Alzheimer Disease Internal medicine mental disorders medicine Acquired Cognitive Impairment Genetics Dementia Humans Genetic Predisposition to Disease Allele Alleles Genetic Association Studies Aged Probability business.industry Prevention Alzheimer’s Disease Genetics Consortium Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) General Chemistry Odds ratio medicine.disease Brain Disorders 030104 developmental biology Good Health and Well Being lcsh:Q business 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk. |
| Databáze: | OpenAIRE |
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