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Record W3176850175 · doi:10.1038/s41467-021-24220-7

Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease

2021· article· en· W3176850175 on OpenAlexafffund
William T. Hu, Tuğba Öztürk, Alexander Kollhoff, Whitney Wharton, J. Christina Howell, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Zaven Kachaturian, Maria Carrillo, William Z. Potter, Lisa L. Barnes, Marie Bernard, Héctor Alfredo Baptista González, Carole Ho, John Hsiao, Eliezer Masliah, Donna Masterman, Ozioma C. Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher, Tom Montine, Jeffrey Kaye, Lisa C. Silbert, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, James B. Brewer, Judith L. Heidebrink, David S. Knopman, Javier Villanueva‐Meyer, Rachelle S. Doody, Joseph S. Kass, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Beau M. Ances, Mark A. Mintun, David Geldmacher, Marissa Natelson Love, Hillel Grossman, Martin Goldstein, Raj C. Shah, Melissa Lamar, Ranjan Duara, Maria T. Greig‐Custo, Marilyn Albert, Chiadi U. Onyike, Amanda Smith, Martin Sadowski, Thomas Wısnıewskı, Melanie Shulman, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Jason Karlawish, David A. Wolk, Charles D. Smith, Gregory A. Jicha, Riham El Khouli, Oscar L. López, Anton P. Porsteinsson, Gaby Thai, Aimee Pierce, Brendan Kelley, Trung Nguyen, Kyle Womack, Allan I. Levey, James J. Lah, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Daniel Silverman, Sarah Kremen, Neill R. Graff‐Radford, Martin R. Farlow, Christopher H. van Dyck, Adam P. Mecca, Howard Chertkow, Susan Vaitekunis, Sandra E. Black, Bojana Stefanovic, Chris Heyn, Ging‐Yuek Robin Hsiung, Vesna Sossi, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Ian Grant, Emily Rogalskı, M.‐Marsel Mesulam, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Howard J. Rosen, Bruce L. Miller, David C. Perry, Raymond Scott Turner, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Christine M. Belden, Alireza Atri, Bryan M. Spann, Ronald Killiany, Robert A. Stern, Jesse Mez, Thomas O. Obisesan, Oyonumo Ntekim, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Vernice Bates, Horacio Capote, Michael Borrie, T.-Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Allison Perrin, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, David Hart, Earl A. Zimmerman, Dzintra Celmins, Del D. Miller, Hristina Koleva, Hyungsub Shim, Jeff D. Williamson, Suzanne Craft, Jo Cleveland, Brian R. Ott, Jonathan Drake, Geoffrey Tremont, Marwan N. Sabbagh, Aaron Ritter, Jacobo Mintzer, Joseph C. Masdeu, Jiong Shi, Paul Newhouse, Steven Potkin, Stephen Salloway, Paul Malloy, Stephen Correia, Smita Kittur, Godfrey D. Pearlson, Karen Blank, Laura A. Flashman, Marc Seltzer, Athena Lee, Norman Relkin, Gloria Chiang

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsParkwood InstituteSt Joseph's Health CareSunnybrook Health Science CentreUniversity of British ColumbiaMcGill University
FundersNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationDoD Alzheimer's Disease Neuroimaging InitiativePfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeNational Center for Advancing Translational SciencesMeso Scale DiagnosticsNational Institute on AgingAlzheimer's AssociationNational Institutes of HealthU.S. Department of Health and Human ServicesFoundation for the National Institutes of Health
KeywordsNeuroinflammationDiseaseMicrogliaCerebrospinal fluidTREM2DementiaAlzheimer's diseaseMedicineReceptorTumor necrosis factor alphaImmunologyInflammationBioinformaticsNeuroscienceBiologyInternal medicine

Abstract

fetched live from OpenAlex

Neuroinflammation is associated with Alzheimer's disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer's Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer's disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer's disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer's markers.

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)0.001
metaresearch head score (Gemma)0.002
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 score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.042
GPT teacher head0.287
Teacher spread0.245 · 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

Citations36
Published2021
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicNeuroinflammation and Neurodegeneration MechanismsFrench-language works237,207