Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
Eric M. Reiman(Alzheimer's Association), Joseph F. Arboleda‐Velásquez(Massachusetts Eye and Ear Infirmary), Yakeel T. Quiroz(Harvard University), Matthew J. Huentelman(Translational Genomics Research Institute), Thomas G. Beach(Alzheimer's Association), Richard J. Caselli(Mayo Clinic in Arizona), Yinghua Chen(Alzheimer's Association), Yi Su(Alzheimer's Association), Amanda Myers(University of Miami), John Hardy(National Hospital for Neurology and Neurosurgery), Jean Paul Vonsattel(NewYork–Presbyterian Hospital), Steven G. Younkin(Mayo Clinic in Florida), David Bennett(Rush University Medical Center), Philip L. De Jager(Columbia University Irving Medical Center), Eric B. Larson(Kaiser Permanente Washington Health Research Institute), Paul K. Crane(University of Washington), C. Dirk Keene(University of Washington), M. Ilyas Kamboh(University of Pittsburgh), Julia Kofler(University of Pittsburgh), Linda Duque(University of Miami), John R. Gilbert(University of Miami), Harry E. Gwirtsman(Vanderbilt University), Joseph D. Buxbaum(Icahn School of Medicine at Mount Sinai), Dennis W. Dickson(Mayo Clinic in Florida), Matthew P. Frosch(Massachusetts General Hospital), Bernardino Ghetti(Indiana University – Purdue University Indianapolis), Kathryn L. Lunetta(Boston University), Li-San Wang(University of Pennsylvania), Bradley T. Hyman(Harvard University), Walter A. Kukull(University of Washington), Tatiana M. Foroud(Indiana University – Purdue University Indianapolis), Jonathan L. Haines(Case Western Reserve University), Richard Mayeux(Columbia University), Margaret A. Pericak‐Vance(University of Miami), Julie A. Schneider(Rush University Medical Center), John Q. Trojanowski(University of Pennsylvania), Lindsay A. Farrer(Boston University), Gerard D. Schellenberg(University of Pennsylvania), Gary W. Beecham(University of Miami), Thomas J. Montine(Stanford University), Gyungah Jun(Boston University), Erin L. Abner(University of Kentucky), Perrie M. Adams(The University of Texas Southwestern Medical Center), Marilyn S. Albert(Johns Hopkins University), Roger L. Albin(Indiana University Health), Liana G. Apostolova(Indiana University Health), Steven E. Arnold(University of Pennsylvania), Sanjay Asthana(University of Wisconsin–Madison), Craig Atwood(University of Wisconsin–Madison), Clinton T. Baldwin(Boston University), Robert C. Barber(University of North Texas), Lisa L. Barnes(Rush University Medical Center), Sandra Barral(Columbia University), James T. Becker(University of Pittsburgh), Duane Beekly(University of Washington), Eileen H. Bigio(Northwestern University), Thomas D. Bird(University of Washington), Deborah Blacker(Massachusetts Eye and Ear Infirmary), Bradley F. Boeve(Mayo Clinic in Arizona), James D. Bowen(Swedish Medical Center), Adam Boxer(University of California, San Francisco), James R. Burke(Duke University), Jeffrey M. Burns(University of Kansas Medical Center), Nigel J. Cairns(Washington University in St. Louis), Laura B. Cantwell(University of Pennsylvania), Chuanhai Cao(University of South Florida), Chris Carlson(Fred Hutch Cancer Center), Cynthia M. Carlsson(University of Wisconsin–Madison), Regina M. Carney(University of Miami), Minerva M. Carrasquillo(Mayo Clinic in Florida), Helena C. Chui(University of Southern California), David H. Cribbs(University of California, Irvine), Elizabeth Crocco(University of Miami), Carlos Cruchaga(Hope Center for Neurological Disorders), Charles DeCarli(University of California, Davis), Malcolm Dick(University of California, Irvine), Rachelle S. Doody(Baylor College of Medicine), Ranjan Duara(Mount Sinai Medical Center), Nilüfer Ertekin‐Taner(Mayo Clinic in Florida), Denis A. Evans(Rush University Medical Center), Kelley Faber(Duke University), Thomas Fairchild(University of North Texas), Kenneth B. Fallon(University of Alabama at Birmingham), David W. Fardo(University of Kentucky), Martin R. Farlow(Indiana University – Purdue University Indianapolis), Steven H. Ferris(New York University), Douglas Galasko(University of California San Diego), Marla Gearing(Emory Healthcare), Daniel H. Geschwind(University of California, Los Angeles), Valentina Ghisays(Alzheimer's Association), Alison Goate(Icahn School of Medicine at Mount Sinai), Neill R. Graff‐Radford(Mayo Clinic in Florida), Robert C. Green(Brigham and Women's Hospital), John H. Growdon(Harvard University), Håkon Håkonarson(Children's Hospital of Philadelphia), Ronald L. Hamilton(University of Pittsburgh), Kara L. Hamilton‐Nelson(University of Miami), Lindy E. Harrell(University of Alabama at Birmingham), Lawrence S. Honig(Columbia University), Ryan M. Huebinger(The University of Texas Southwestern Medical Center), Christine M. Hulette(Duke University), Gail P. Jarvik(University of Washington), Lee‐Way Jin(University of California, Davis), Anna Karydas(University of California, San Francisco), Mindy J. Katz(Albert Einstein College of Medicine), John Kauwe(Brigham Young University), Jeffrey A. Kaye(Oregon Health & Science University), Ronald Kim(University of California, Irvine), Neil W. Kowall(Boston University), Joel H. Kramer(University of California, San Francisco), Brian W. Kunkle(University of Miami), Amanda P. Kuzma(University of Pennsylvania), Frank M. LaFerla(University of California, Irvine), James J. Lah(Emory University), Yuk Yee Leung(University of Pennsylvania), James B. Leverenz(Cleveland Clinic), Allan I. Levey(Emory University), Ge Li(University of Washington), Andrew P. Lieberman(University of Michigan), Richard Lipton(Albert Einstein College of Medicine), Oscar L. López(University of Pittsburgh), Constantine G. Lyketsos(Johns Hopkins University), John Malamon(University of Pennsylvania), Daniel Marson(University of Alabama at Birmingham), Eden R. Martin(University of Miami), Frank Martiniuk(New York University), Deborah C. Mash(University of Miami), Eliezer Masliah(University of California San Diego), Wayne C. McCormick(University of Washington), Susan M. McCurry(University of Washington), Andrew McDavid(Fred Hutch Cancer Center), Stefan McDonough(Pfizer (United States)), Ann C. McKee(Boston University), Marsel Mesulam(Northwestern University), Bruce L. Miller(University of California, San Francisco), Carol A. Miller(University of Southern California), Joshua W. Miller(University of California, Davis), John C. Morris(Washington University in St. Louis), Shubhabrata Mukherjee(University of Washington), Adam C. Naj(University of Pennsylvania), Sid E. O’Bryant(University of North Texas), John Olichney(University of California, Davis), Joseph E. Parisi(Mayo Clinic in Arizona), Henry L. Paulson(University of Michigan), Elaine R. Peskind(University of Washington), Ronald Petersen(Mayo Clinic in Arizona), Aimee Pierce(University of California, Irvine), Wayne W. Poon(University of California, Irvine), Huntington Potter(University of Colorado Denver), Liming Qu(University of Pennsylvania), Joseph F. Quinn(Oregon Health & Science University), Ashok Raj(Indiana University – Purdue University Indianapolis), Murray A. Raskind(University of Washington), Barry Reisberg(New York University), Joan Reisch(The University of Texas Southwestern Medical Center), Christiane Reitz(Columbia University), John M. Ringman(University of Southern California), Erik D. Roberson(University of Alabama at Birmingham), Ekaterina Rogaeva(University of Toronto), Howard J. Rosen(University of California, San Francisco), Roger N. Rosenberg(The University of Texas Southwestern Medical Center), Donald R. Royall(Veterans Health Administration), Mark A. Sager(University of Wisconsin–Madison), Mary Sano(Icahn School of Medicine at Mount Sinai), Andrew J. Saykin(Indiana University – Purdue University Indianapolis), Lon S. Schneider(University of Southern California), William W. Seeley(University of California, San Francisco), Amanda Smith(University of South Florida), Joshua A. Sonnen(University of Washington), Salvatore Spina(Indiana University – Purdue University Indianapolis), Peter St George‐Hyslop(University of Toronto), Robert A. Stern(Boston University), Russell H. Swerdlow(University of Kansas Medical Center), Rudolph E. Tanzi(Harvard University), Juan C. Troncoso(Johns Hopkins University), Debby W. Tsuang(University of Washington), Otto Valladares(University of Pennsylvania), Vivianna M. Van Deerlin(University of Pennsylvania), Linda J. Van Eldik(University of Kentucky), Badri N. Vardarajan(Columbia University), Harry V. Vinters(University of California, Los Angeles), Sandra Weıntraub(Northwestern University), Kathleen A. Welsh‐Bohmer(Duke University), Kirk C. Wilhelmsen(University of North Carolina at Chapel Hill), Jennifer Williamson(Columbia University), Thomas S. Wingo(Emory University), Randall L. Woltjer(Oregon Health & Science University), Clinton B. Wright(University of Miami), Chuang-Kuo Wu(Texas Tech University), Chang‐En Yu(University of Washington), Lei Yu(Rush University Medical Center), Yi Zhao(University of Pennsylvania)
Cited by 484Open Access
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.
Related Papers
No related papers found
Powered by citation graph analysis