ArticleNature neuroscience2025
Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex.
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Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43citing papers in PubMed
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Who cites it
43 citing papers in PubMed.
- Global and regional amyloid-β in explaining APOE-ε4 and sex associations with medial temporal tau: a neuropathology study.Acta neuropathologica · 2026Article
- Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Associations of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- [European journal of nuclear medicine and molecular imaging · 2026Article
- A Harmonized Visual Reading Framework for Tau PET Staging in Alzheimer Disease.JAMA neurology · 2026Article
- Modelling the temporal evolution of plasma p-tau217, amyloid PET, tau PET and cognition.Brain : a journal of neurology · 2026Article
- Mapping sex-specific associations of adiposity with age-related cognitive decline and multimodal Alzheimer's pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Top five Alzheimer Disease trial eligibility criteria favor men compared to women in a clinic-based cohort.The journal of prevention of Alzheimer's disease · 2026Observational
- CSF and plasma tau biomarkers in the Down syndrome-Alzheimer's disease continuum.EBioMedicine · 2026Article
- Tau-PET and CSF MTBR-tau243 comparisons validate increased tau aggregation in females.European journal of nuclear medicine and molecular imaging · 2026Article
- Biomarker-Based Diagnosis and Care Pathways for Alzheimer's Disease in the Era of Disease-Modifying Treatments: A Consensus Statement by Belgian Experts.European journal of neurology · 2026Article
- The clinical Alzheimer's disease spectrum classified in the A/T/N framework withEuropean journal of nuclear medicine and molecular imaging · 2026Observational
- Considerations in Alzheimer's Disease in Women.Current neurology and neuroscience reports · 2026Review
- A probabilistic framework for clinicopathological Alzheimer's disease using tau-PET.Alzheimer's research & therapy · 2026Article
- Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study.Alzheimer's research & therapy · 2026Article
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Imaging Genomics Across Primate Species: Advancing Understanding of Neurological and Psychiatric Disorders.Neuroscience bulletin · 2026Review
- A clinically feasible framework to estimate tau pathology and clinical-biological discordance in the Alzheimer's disease spectrum.Alzheimer's research & therapy · 2026Article
- Generating synthetic tau-PET scans in Alzheimer's disease from MRI, blood biomarkers and demographics with deep learning.medRxiv : the preprint server for health sciences · 2026Article
- Correlation between in vivoAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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Authors and funding
99 authors.
Rik Ossenkoppele *Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. r.ossenkoppele@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-1584-7477
Emma M Coomans *Alzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.
Liana G ApostolovaIndiana University School of Medicine, Indianapolis, IN, USA.
Suzanne L BakerLawrence Berkeley National Laboratory, Berkeley, CA, USA.
Henryk BarthelDepartment of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
Tammy L S BenzingerDepartment of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8114-0552
Tobey BetthauserWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-8856-1352
Gérard N BischofFaculty of Medicine, University of Cologne and Department of Nuclear Medicine University Hospital Cologne, Cologne, Germany.
Michel BottlaenderUniversité Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, INSERM, Orsay, France.ORCID http://orcid.org/0000-0002-2890-3653
Pierick BourgeatAustralian eHealth Research Centre, CSIRO, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-2605-4766
Anouk den BraberAlzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.
Matthias BrendelDepartment of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-9247-2843
Adam M BrickmanGertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-5125-8226
David M CashDementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-7833-616X
Maria C CarrilloMedical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
William CoathDementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Bradley T ChristianWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-9653-559X
Brad C DickersonFrontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5958-3445
Vincent DoreAustralian eHealth Research Centre, CSIRO, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-8051-0558
Alexander DrzezgaFaculty of Medicine, University of Cologne and Department of Nuclear Medicine University Hospital Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0001-6018-716X
Azadeh FeizpourDepartment of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, Australia.ORCID http://orcid.org/0000-0003-0826-4011
Wiesje M van der FlierAlzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8766-6224
Nicolai FranzmeierMunich Cluster for Systems Neurology (SyNergy), Munich, Germany.ORCID http://orcid.org/0000-0001-9736-2283
Giovanni B FrisoniMemory Clinic, Geneva University Hospitals, Geneva, Switzerland.
Valentina GaribottoDivision of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland.
Elsmarieke van de GiessenNeurodegeneration, Amsterdam Neuroscience, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9956-4233
Juan Domingo-GispertBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Johannes GnoerichDepartment of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0003-1554-7765
Yuna GuDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Yihui GuanDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Bernard J HanseeuwInstitute of Neuroscience, UCLouvain, Brussels, Belgium.
Theresa M HarrisonDepartment of Neuroscience, University of California Berkeley, Berkeley, CA, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-7916-622X
Elena JaegerDepartment of Nuclear Medicine, University of Cologne, University Hospital of Cologne, Cologne, Germany.ORCID http://orcid.org/0009-0007-9387-3175
William J JagustDepartment of Neuroscience, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4458-113X
Willemijn J JansenAlzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Renaud La JoieMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2581-8100
Keith A JohnsonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sterling C JohnsonWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-8501-545X
Ian A KennedyEli Lilly and Company, Indianapolis, IN, USA.
Jun Pyo KimDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-4376-3107
Koen van LaereDepartment of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-5200-7245
Julien LagardeUniversité Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, INSERM, Orsay, France.ORCID http://orcid.org/0000-0002-2018-261X
Patrick LaoDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
José A LuchsingerDepartments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY, USA.
Silke KernDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
William C KreislDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Vincent MalotauxInstitute of Neuroscience, UCLouvain, Brussels, Belgium.
Maura MalpettiDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-8923-9656
Jennifer J ManlyDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Xiaoxie MaoDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-8885-7724
Mayo Clinic Study on Aging
Konstantin MesserschmidtDepartment of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany.
Carolina MinguillonBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Elizabeth M MorminoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
John T O'BrienDepartment of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.ORCID http://orcid.org/0000-0002-0837-5080
Sebastian PalmqvistClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-9267-1930
Debora E PerettiLaboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-3033-8817
Ron C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-8178-6601
Yolande A L PijnenburgAlzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.
Michael J PontecorvoEli Lilly and Company, Indianapolis, IN, USA.
Judes PoirierDouglas Mental Health University Institute, Centre for Studies on the Prevention of Alzheimer's Disease (StoP-AD), Montréal, Québec, Canada.ORCID http://orcid.org/0000-0002-8018-4545
PREVENT-AD Research Group
Gil D RabinoviciMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3626-4265
Nesrine RahmouniTranslational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montréal, Québec, Canada.
Shannon L RisacherIndiana University, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-3304-7943
Pedro Rosa-NetoTranslational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montréal, Québec, Canada.ORCID http://orcid.org/0000-0001-9116-1376
Howard RosenMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Christopher C RoweDepartment of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, Australia.ORCID http://orcid.org/0000-0003-3910-2453
James B RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7216-8679
Michael RullmannClinic for Cognitive Neurology, University Hospital of Leipzig and Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Yasmine SalmanInstitute of Neuroscience, UCLouvain, Brussels, Belgium.ORCID http://orcid.org/0000-0002-8564-5136
Marie SarazinUniversité Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, INSERM, Orsay, France.
Andrew J SaykinIndiana University, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-1376-8532
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-9482-1752
Michael SchöllWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0001-7800-1781
Jonathan M SchottDementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0003-2059-024X
Sang Won SeoDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, USA.
Sergey ShcherbininEli Lilly and Company, Indianapolis, IN, USA.
Mahnaz ShekariBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Ingmar SkoogDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Ruben SmithClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-7147-0112
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Laure SpruytLaboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-0618-5005
Erik StomrudClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Olof StrandbergClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Joseph TherriaultTranslational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montréal, Québec, Canada.
Fang XieDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-2667-281X
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-6237-2502
Victor L VillemagneDepartment of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, Australia.
Sylvia VilleneuveDouglas Mental Health University Institute, Centre for Studies on the Prevention of Alzheimer's Disease (StoP-AD), Montréal, Québec, Canada.ORCID http://orcid.org/0000-0003-2338-0467
Pieter Jelle VisserAlzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8008-9727
Hillary VosslerDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0009-0007-8693-1939
Christina B YoungDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Colin GrootAlzheimer Center Amsterdam, Neurology, Amsterdam UMC; location VUmc, Amsterdam, The Netherlands.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.ORCID http://orcid.org/0000-0001-8467-7286
Funding
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS, Suzanne Elizabeth Schindler · 1985 to 2026
$69.5MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1MStanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI ELIZABETH MORMINO · 2020 to 2026
$29.0MDisease pathways in the population determined by amyloid, tau, and neurodegeneration imaging biomarkersR37AG011378 · NIA · MAYO CLINIC ROCHESTER · PI CLIFFORD R. JACK · 2018 to 2026
$6.8MUnderstanding the mechanisms linking small vessel cerebrovascular disease and Alzheimer's disease pathophysiology with neurodegeneration and cognition during midlifeR00AG065506 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LAO, PATRICK JORDAN · 2023 to 2025
$742kLinking basal forebrain and entorhinal cortex vulnerability to preclinical Alzheimer's diseaseK01AG078443 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI Theresa M. Harrison · 2022 to 2026
$656kRegional tau deposition and digital assessment of cognition in preclinical AD and MCIK99AG071837 · NIA · STANFORD UNIVERSITY · PI YOUNG, CHRISTINA B · 2022 to 2023
$256kNIA NIH HHS K01 AG078443NIA NIH HHS K99 AG071837NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066515NIA NIH HHS R00 AG065506NIA NIH HHS R37 AG011378NIA NIH HHS U01 AG057195
Abstract
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).
Indexed as
Amyloid beta-PeptidesApolipoproteins ECognitive Dysfunctiontau ProteinsAgedAged, 80 and overAge FactorsCohort StudiesFemaleGenotypeHumansMaleMiddle AgedPositron-Emission TomographySex FactorsAmyloid beta-PeptidesApolipoproteins Etau Proteins
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