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Record W4412470623 · doi:10.1038/s41593-025-02000-6

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex

2025· article· en· W4412470623 on OpenAlexafffund
Rik Ossenkoppele, Emma M. Coomans, Liana G. Apostolova, Suzanne L. Baker, Henryk Barthel, Thomas G. Beach, Tammie L.S. Benzinger, Tobey J. Betthauser, Gérard N. Bischof, Michel Bottlaender, Pierrick Bourgeat, Anouk den Braber, Matthias Brendel, Adam M. Brickman, David M. Cash, María C. Carrillo, William Coath, Bradley T. Christian, Bradford C. Dickerson, Vincent Doré, Alexander Drzezga, Azadeh Feizpour, Wiesje M. van der Flier, Nicolai Franzmeier, Giovanni B. Frisoni, Valentina Garibotto, Elsmarieke van de Giessen, Juan Domingo-Gispert, Johannes Gnörich, Yuna Gu, Yihui Guan, Bernard Hanseeuw, Theresa M. Harrison, Clifford R. Jack, Elena Jaeger, William J. Jagust, Willemijn J. Jansen, Renaud La Joie, Keith A. Johnson, Sterling C. Johnson, Ian Kennedy, Jun Pyo Kim, Koen Van Laere, Julien Lagarde, Patrick J. Lao, José A. Luchsinger, Silke Kern, William Charles Kreisl, Vincent Malotaux, Maura Malpetti, Jennifer J. Manly, Xiaoxie Mao, Niklas Mattsson, Ronald C. Petersen, Konstantin Messerschmidt, Carolina Minguillón, Sebastian Palmqvist, Débora Elisa Peretti, Yolande A.L. Pijnenburg, Michael J. Pontecorvo, Judes Poirier, Gil D. Rabinovici, Nesrine Rahmouni, Shannon L. Risacher, Pedro Rosa‐Neto, Howard Rosen, Christopher C. Rowe, James B. Rowe, Michael Rullmann, Yasmine Salman, Marie Sarazin, Andrew J. Saykin, Julie A. Schneider, Michael Schöll, Jonathan M. Schott, Sang Won Seo, Geidy E. Serrano, Sergey Shcherbinin, Mahnaz Shekari, Ingmar Skoog, Ruben Smith, Reisa A. Sperling, Laure Spruyt, Erik Stomrud, Olof Strandberg, Joseph Therriault, Fang Xie, Rik Vandenberghe, Victor L. Villemagne, Sylvia Villeneuve, Pieter Jelle Visser, Hillary Vossler, Christina B. Young

Bibliographic record

VenueNature Neuroscience · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsMcGill UniversityDouglas Mental Health University Institute
FundersNational Institute on AgingInstitut de Recherches ServierNational Health and Medical Research CouncilCanadian Institutes of Health ResearchIrving Medical Center, Columbia UniversityAvid RadiopharmaceuticalsParkinsonfondenEMD SeronoAstraZenecaEuropean CommissionFondation pour la Recherche sur AlzheimerGenentechNational Institutes of HealthArizona Biomedical Research CommissionKnut och Alice Wallenbergs StiftelseIXICOH. Lundbeck A/SSkånes universitetssjukhusAlzheimer's Disease Neuroimaging InitiativeStichting DioraphteKonung Gustaf V:s och Drottning Victorias FrimurarestiftelseNovo NordiskServierVetenskapsrådetUniversity of Southern CaliforniaEisaiAustralian GovernmentLunds UniversitetAlzheimerfondenGovernment of CanadaZonMwU.S. Department of DefenseCommonwealth Scientific and Industrial Research OrganisationAlzheimer SocietyAlzheimer NederlandCerveau TechnologiesPfizer CanadaFondation Brain CanadaGHR FoundationProthenaAlzheimer's AssociationArizona Department of Health ServicesMerck KGaANorthern California Institute for Research and EducationMcGill UniversityPfizerBiogenBioClinicaF. Hoffmann-La RocheEli Lilly and CompanyBristol-Myers SquibbNovartis Pharmaceuticals CorporationMeso Scale DiagnosticsCure Alzheimer's FundSanofi
KeywordsApolipoprotein EGenotypeCognitive impairmentNeurosciencePsychologyAmyloid (mycology)CognitionPet imagingMedicineClinical psychologyDevelopmental psychologyBiologyDiseaseInternal medicinePositron emission tomographyPathologyGeneticsGene

Abstract

fetched live from OpenAlex

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, APOE ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. APOE ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (N = 5,072 from 3 cohorts).

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.004
Threshold uncertainty score0.618

Codex and Gemma teacher scores by category

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

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 head0.009
GPT teacher head0.311
Teacher spread0.302 · 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 teacher head, 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

Citations37
Published2025
Admission routes2
Has abstractyes

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