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

Reiman, Eric M.; Arboleda‐Velásquez, Joseph F.; Quiroz, Yakeel T.; Huentelman, Matthew J.; Beach, Thomas G.; Caselli, Richard J.; Chen, Yinghua; Su, Yi; Myers, Amanda; Hardy, John; Vonsattel, Jean Paul; Younkin, Steven G.; Bennett, David; Jager, Philip L. De; Larson, Eric B.; Crane, Paul K.; Keene, C. Dirk; Kamboh, M. Ilyas; Kofler, Julia; Duque, Linda; Gilbert, John R.; Gwirtsman, Harry E.; Buxbaum, Joseph D.; Dickson, Dennis W.; Frosch, Matthew P.; Ghetti, Bernardino; Lunetta, Kathryn L.; Wang, Li-San; Hyman, Bradley T.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Mayeux, Richard; Pericak‐Vance, Margaret A.; Schneider, Julie A.; Trojanowski, John Q.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Beecham, Gary W.; Montine, Thomas J.; Jun, Gyungah; Abner, Erin L.; Adams, Perrie M.; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Asthana, Sanjay; Atwood, Craig; Baldwin, Clinton T.; Barber, Robert C.; Barnes, Lisa L.; Barral, Sandra; Becker, James T.; Beekly, Duane; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boeve, Bradley F.; Bowen, James D.; Boxer, Adam; Burke, James R.; Burns, Jeffrey M.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carlson, Chris; Carlsson, Cynthia M.; Carney, Regina M.; Carrasquillo, Minerva M.; Chui, Helena C.; Cribbs, David H.; Crocco, Elizabeth; Cruchaga, Carlos; DeCarli, Charles; Dick, Malcolm; Doody, Rachelle S.; Duara, Ranjan; Ertekin‐Taner, Nilüfer; Evans, Denis A.; Faber, Kelley; Fairchild, Thomas; Fallon, Kenneth B.; Fardo, David W.; Farlow, Martin R.; Ferris, Steven H.; Galasko, Douglas; Gearing, Marla; Geschwind, Daniel H.; Ghisays, Valentina; Goate, Alison; Graff‐Radford, Neill R.; Green, Robert C.; Growdon, John H.; Håkonarson, Håkon; Hamilton, Ronald L.; Hamilton‐Nelson, Kara L.; Harrell, Lindy E.; Honig, Lawrence S.; Huebinger, Ryan M.; Hulette, Christine M.; Jarvik, Gail P.; Jin, Lee‐Way; Karydas, Anna; Katz, Mindy J.; Kauwe, John; Kaye, Jeffrey A.; Kim, Ronald; Kowall, Neil W.; Kramer, Joel H.; Kunkle, Brian W.; Kuzma, Amanda P.; LaFerla, Frank M.; Lah, James J.; Leung, Yuk Yee; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lieberman, Andrew P.; Lipton, Richard; López, Oscar L.; Lyketsos, Constantine G.; Malamon, John; Marson, Daniel; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McCormick, Wayne C.; McCurry, Susan M.; McDavid, Andrew; McDonough, Stefan; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Morris, John C.; Mukherjee, Shubhabrata; Naj, Adam C.; O’Bryant, Sid E.; Olichney, John; Parisi, Joseph E.; Paulson, Henry L.; Peskind, Elaine R.; Petersen, Ronald; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Qu, Liming; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray A.; Reisberg, ‌Barry; Reisch, Joan; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rogaeva, Ekaterina; Rosen, Howard J.; Rosenberg, Roger N.; Royall, Donald R.; Sager, Mark A.; Sano, Mary; Saykin, Andrew J.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda; Sonnen, Joshua A.; Spina, Salvatore; George‐Hyslop, Peter St; Stern, Robert A.; Swerdlow, Russell H.; Tanzi, Rudolph E.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Deerlin, Vivianna M. Van; Eldik, Linda J. Van; Vardarajan, Badri N.; Vinters, Harry V.; Weıntraub, Sandra; Welsh‐Bohmer, Kathleen A.; Wilhelmsen, Kirk C.; Williamson, Jennifer; Wingo, Thomas S.; Woltjer, Randall L.; Wright, Clinton B.; Wu, Chuang-Kuo; Yu, Chang‐En; Yu, Lei; Zhao, Yi

doi:10.1038/s41467-019-14279-8

articleNature CommunicationsFeb 3, 2020GOLD OA

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

EMEric M. Reiman JFJoseph F. Arboleda‐Velásquez YTYakeel T. Quiroz MJMatthew J. Huentelman TGThomas G. Beach

Alzheimer's Association · Translational Genomics Research Institute · +81 more institutions

PubMed

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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…

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Topics

Keywords

Dementia
Medicine
Neuroscience
Gerontology
Biology
Genetics
Bioinformatics
Psychiatry

UN Sustainable Development Goals

Good health and well-being

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