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Record W3003860558 · doi:10.1038/s41467-019-14279-8

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

2020· article· en· W3003860558 on OpenAlexafffund
Eric M. Reiman, Joseph F. Arboleda‐Velásquez, Yakeel T. Quiroz, Matthew J. Huentelman, Thomas G. Beach, Richard J. Caselli, Yinghua Chen, Yi Su, Amanda Myers, John Hardy, Jean Paul Vonsattel, Steven G. Younkin, David Bennett, Philip L. De Jager, Eric B. Larson, Paul K. Crane, C. Dirk Keene, M. Ilyas Kamboh, Julia Kofler, Linda Duque, John R. Gilbert, Harry E. Gwirtsman, Joseph D. Buxbaum, Dennis W. Dickson, Matthew P. Frosch, Bernardino Ghetti, Kathryn L. Lunetta, Li-San Wang, Bradley T. Hyman, Walter A. Kukull, Tatiana M. Foroud, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak‐Vance, Julie A. Schneider, John Q. Trojanowski, Lindsay A. Farrer, Gerard D. Schellenberg, Gary W. Beecham, Thomas J. Montine, Gyungah Jun, Erin L. Abner, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Clinton T. Baldwin, Robert C. Barber, Lisa L. Barnes, Sandra Barral, James T. Becker, Duane Beekly, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Jeffrey M. Burns, Nigel J. Cairns, Laura B. Cantwell, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Helena C. Chui, David H. Cribbs, Elizabeth Crocco, Carlos Cruchaga, Charles DeCarli, Malcolm Dick, Rachelle S. Doody, Ranjan Duara, Nilüfer Ertekin‐Taner, Denis A. Evans, Kelley Faber, Thomas Fairchild, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Steven H. Ferris, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, Valentina Ghisays, Alison Goate, Neill R. Graff‐Radford, Robert C. Green, John H. Growdon, Håkon Håkonarson, Ronald L. Hamilton, Kara L. Hamilton‐Nelson, Lindy E. Harrell, Lawrence S. Honig, Ryan M. Huebinger, Christine M. Hulette, Gail P. Jarvik, Lee‐Way Jin, Anna Karydas, Mindy J. Katz, John Kauwe, Ronald Kim, Neil W. Kowall, Joel H. Kramer, Brian W. Kunkle, Amanda P. Kuzma, Frank M. LaFerla, James J. Lah, Yuk Yee Leung, James B. Leverenz, Allan I. Levey, Ge Li, Andrew P. Lieberman, Richard Lipton, Oscar L. López, Constantine G. Lyketsos, John Malamon, Daniel Marson, Eden R. Martin, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew McDavid, Stefan McDonough, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, John C. Morris, Shubhabrata Mukherjee, Adam C. Naj, Sid E. O’Bryant, John Olichney, Joseph E. Parisi, Henry L. Paulson, Elaine R. Peskind, Ronald Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Liming Qu, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, ‌Barry Reisberg, Joan Reisch, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Lon S. Schneider, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Peter St George‐Hyslop, Robert A. Stern, Russell H. Swerdlow, Rudolph E. Tanzi, Juan C. Troncoso, Debby W. Tsuang, Otto Valladares, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Randall L. Woltjer, Clinton B. Wright, Chuang-Kuo Wu, Chang‐En Yu, Lei Yu, Yi Zhao

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersUniversity of Colorado School of Medicine, Anschutz Medical CampusNIH Clinical CenterNational Institute on AgingGeriatric Research Education and Clinical CenterFeinberg School of MedicinePerelman School of Medicine, University of PennsylvaniaUniversity of California, Los AngelesUniversity of California, IrvineArizona Biomedical Research CommissionRosetrees TrustNorthwestern UniversityPfizerYork UniversityUniversity of Southern CaliforniaBrigham Young UniversityHope Center for Neurological DisordersUSF Health Byrd Alzheimer's InstituteUniversity of South FloridaNational Institute of Neurological Disorders and StrokeUniversity of PittsburghJohns Hopkins UniversityUniversity of WashingtonNational Center for Advancing Translational SciencesMedical Research CouncilUniversity of North TexasNancy and Buster Alvord EndowmentCleveland ClinicParkinson's UKBrigham and Women's HospitalMichael J. Fox Foundation for Parkinson's ResearchEmory UniversityUniversity of PennsylvaniaChildren's Hospital of PhiladelphiaArizona Department of Health ServicesRush UniversityUniversity of California, San DiegoU.S. Department of Veterans AffairsU.S. Department of Health and Human Services
KeywordsDementiaMedicineNeuroscienceGerontologyBiologyGeneticsBioinformaticsPsychiatryPsychologyPathologyDisease

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.075
GPT teacher head0.354
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations490
Published2020
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicAlzheimer's disease research and treatmentsFrench-language works237,207