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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.
Afiliação
  • Reiman EM; Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, 901 E Willetta Street, Phoenix, AZ, 85006, USA. eric.reiman@bannerhealth.com.
  • Arboleda-Velasquez JF; University of Arizona, 714 E Van Buren Street, Phoenix, AZ, 85006, USA. eric.reiman@bannerhealth.com.
  • Quiroz YT; Arizona State University, 522 N Central Avenue, Phoenix, AZ, 85004, USA. eric.reiman@bannerhealth.com.
  • Huentelman MJ; Neurogenomics Division, Translational Genomics Research Institute and Arizona Alzheimer's Consortium, 445 N Fifth Street, Phoenix, AZ, 85004, USA. eric.reiman@bannerhealth.com.
  • Beach TG; Schepens Eye Research Institute of Mass Eye and Ear and the Department of Ophthalmology at Harvard Medical School, 20 Staniford Street, Boston, MA, 02114, USA.
  • Caselli RJ; Departments of Psychiatry and Neurology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Chen Y; Neurogenomics Division, Translational Genomics Research Institute and Arizona Alzheimer's Consortium, 445 N Fifth Street, Phoenix, AZ, 85004, USA.
  • Su Y; Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, 901 E Willetta Street, Phoenix, AZ, 85006, USA.
  • Myers AJ; Mayo Clinic, 13400 E Shea Boulevard, Scottsdale, AZ, 85259, USA.
  • Hardy J; Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, 901 E Willetta Street, Phoenix, AZ, 85006, USA.
  • Paul Vonsattel J; Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, 901 E Willetta Street, Phoenix, AZ, 85006, USA.
  • Younkin SG; Department of Psychiatry and Behavioral Science, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL, 33136, USA.
  • Bennett DA; Department of Molecular Neuroscience, UCL, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
  • De Jager PL; New York Brain Bank and Department of Pathology, New York-Presbyterian Hospital at Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA.
  • Larson EB; Departments of Neuroscience and Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Crane PK; Departments of Neurological Sciences and Pathology (Neuropathology), and Rush Alzheimer's Disease Center, Rush University Medical Center, 1725 W Harrison Street, Chicago, IL, 60612, USA.
  • Keene CD; Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, 710 West 168th Street, New York, NY, 10032, USA.
  • Kamboh MI; Kaiser Permanente Washington Health Research Institute, 1730 Minor Avenue, Seattle, WA, 98101, USA.
  • Kofler JK; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98198, USA.
  • Duque L; Department of Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98198, USA.
  • Gilbert JR; Department of Human Genetics, Alzheimer's Disease Research Center, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
  • Gwirtsman HE; Department of Pathology (Neuropathology), University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
  • Buxbaum JD; Department of Neurology, University of Miami, 1120 NW 14th Street, Miami, FL, 33136, USA.
  • Dickson DW; John P. Hussman Institute for Human Genomics, Department of Human Genetics, and Dr. John T. Macdonald Foundation, University of Miami, 1501 NW 10th Avenue, Miami, FL, 33136, USA.
  • Frosch MP; Department of Psychiatry, Vanderbilt University, 1601 23rd Avenue South, Nashville, TN, 37212, USA.
  • Ghetti BF; Departments of Psychiatry, Neuroscience and Genetics and Genomic Sciences, Mount Sinai School of Medicine, 1468 Madison Avenue, New York, NY, 10029, USA.
  • Lunetta KL; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Wang LS; C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA, 02129, USA.
  • Hyman BT; Department of Pathology and Laboratory Medicine, Indiana University, 340 West 10th Street, Indianapolis, IN, 46202, USA.
  • Kukull WA; Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
  • Foroud T; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
  • Haines JL; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
  • Mayeux RP; Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
  • Pericak-Vance MA; Department of Medical and Molecular Genetics, Indiana University, 410W 10th Street, Indianapolis, IN, 46202, USA.
  • Schneider JA; Institute for Computational Biology and Department of Population and Quantitative Health Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
  • Trojanowski JQ; Taub Institute on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center Department of Neurology, Columbia University, 710 West 168th Street, New York, NY, 10032, USA.
  • Farrer LA; John P. Hussman Institute for Human Genomics, Department of Human Genetics, and Dr. John T. Macdonald Foundation, University of Miami, 1501 NW 10th Avenue, Miami, FL, 33136, USA.
  • Schellenberg GD; Departments of Neurological Sciences and Pathology (Neuropathology), and Rush Alzheimer's Disease Center, Rush University Medical Center, 1725 W Harrison Street, Chicago, IL, 60612, USA.
  • Beecham GW; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
  • Montine TJ; Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
  • Jun GR; Biomedical Genetics Section, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.
Nat Commun ; 11(1): 667, 2020 02 03.
Article em En | MEDLINE | ID: mdl-32015339
ABSTRACT
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Apolipoproteína E2 / Doença de Alzheimer / Homozigoto Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Apolipoproteína E2 / Doença de Alzheimer / Homozigoto Tipo de estudo: Prognostic_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Ano de publicação: 2020 Tipo de documento: Article