ArticlemedRxiv : the preprint server for health sciences2026
Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer's disease.
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Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
55 authors.
Konstantinos ChiotisMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Ganna BlazhenetsMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
David N Soleimani-MeigooniMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Paul S AisenAlzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California; San Diego, California 92121, USA.
Alinda AmuiriMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Alireza AtriBanner Sun Health Research Institute; Sun City, Arizona 85351, USA.
Laurel BeckettDepartment of Public Health Sciences, University of California - Davis; Davis, California 95616, USA.
Michael BrickhouseFrontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School; Boston, Massachusetts 02129, USA.
David G ClarkDepartment of Neurology, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Jeffrey L DageDepartment of Neurology, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida; Jacksonville, Florida 32224, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center; Miami, Florida 33140, USA.
Ani EloyanCenter for Biostatistics and Health Data Science, Brown University; Providence, Rhode Island 02912, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Neill R Graff-RadfordDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Ian M GrantDepartment of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University; Chicago, Illinois 60611, USA.
Dustin B HammersDepartment of Neurology, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Lawrence S HonigTaub Institute and Department of Neurology, Columbia University Irving Medical Center; New York, New York 10032, USA.
Erik C B JohnsonDepartment of Neurology, Emory University School of Medicine; Atlanta, Georgia 30307, USA.
David T JonesDepartment of Neurology, Mayo Clinic; Rochester, Minnesota 55905, USA.
Kala KirbyDepartment of Neurology, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Robert KoeppeDivision of Nuclear Medicine, Department of Radiology, University of Michigan; Ann Arbor, Michigan 48109-5610, USA.
Joel H KramerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Walter A KukullDepartment of Epidemiology, University of Washington; Seattle, Washington 98105, USA.
Julien LagardeMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Antoine LeuzyWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg; Gothenburg, Sweden.
Piyush MaitiMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Joseph C MasdeuNantz National Alzheimer Center, Houston Methodist Neurological Institute and Weill Cornell Medicine; Houston, Texas 77030, USA.
Mario F MendezDepartment of Neurology, David Geffen School of Medicine at UCLA; Los Angeles, California 90095, USA.
Erik MusiekDepartment of Neurology, Washington University in St. Louis; St. Louis, Missouri 63130, USA.
Kelly N NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine; Baltimore, Maryland 21205, USA.
Meghan RiddleDepartment of Neurology, Alpert Medical School, Brown University; Providence, Rhode Island 02912, USA.
Salma RochaMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Emily RogalskiHealthy Aging & Alzheimer's Research Care Center, Department of Neurology, University of Chicago; Chicago, Illinois 60637, USA.
Stephen SallowayDepartment of Neurology, Alpert Medical School, Brown University; Providence, Rhode Island 02912, USA.
Daniel R SchonhautMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Sharon ShaDepartment of Neurology & Neurological Sciences, Stanford University; Palo Alto, California 94304, USA.
Ranjani ShankarMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Alexander TauroneCenter for Biostatistics and Health Data Science, Brown University; Providence, Rhode Island 02912, USA.
Maryanne ThangarajahCenter for Biostatistics and Health Data Science, Brown University; Providence, Rhode Island 02912, USA.
Arthur W TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC; Los Angeles, California 90033, USA.
Alexandra TouroutoglouFrontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School; Boston, Massachusetts 02129, USA.
Raymond Scott TurnerDepartment of Neurology, Georgetown University; Washington D.C. 20057, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic; Rochester, Minnesota 55902, USA.
Thomas S WingoDepartment of Neurology, Emory University School of Medicine; Atlanta, Georgia 30307, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA.
Kyle WomackDepartment of Neurology, Washington University in St. Louis; St. Louis, Missouri 63130, USA.
Jiaxiuxiu ZhangMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association; Chicago, Illinois 60603, USA.
Bradford C DickersonFrontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School; Boston, Massachusetts 02129, USA.
Liana G ApostolovaDepartment of Neurology, Indiana University School of Medicine; Indianapolis, Indiana 46202, USA.
Renaud La JoieMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Gil D RabinoviciMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; San Francisco, California 94143, USA.
Longitudinal Early-onset Alzheimer’s Disease Study consortium and the Alzheimer’s Disease Neuroimaging Initiative
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI Duygu Tosun-Turgut · 2016 to 2026
$226.7MADRC Consortium for Clarity in ADRD Research Through ImagingU01AG082350 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sarah Biber, BRADFORD C DICKERSON · 2023 to 2026
$90.0MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9MResearch Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5MA Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis and Assess Markers of DiseaseU01NS120901 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stacey Lynn Clardy · 2021 to 2026
$19.6MRisk and Resilience, Clinical presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project IIR01NS139383 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Michael Alosco, Nicholas Ashton · 2024 to 2026
$9.3MEarly Onset Alzheimer's Disease ConsortiumR56AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2017 to 2017
$7.7MBiomarker Evaluation in Young Onset Dementia from Diverse Populations (BEYONDD)R56AG075744 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L., BYRD, DESIREE A · 2022 to 2022
$6.1MReimagining Precision Medicine Approaches to AD DiagnosisR35AG072362 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI POSSIN, KATHERINE LAUREL, RABINOVICI, GIL DAN · 2021 to 2025
$4.8MBio-RaPID: Biomarkers and Rates of Progression In Dementia.R01AG089380 · NIA · MAYO CLINIC JACKSONVILLE · PI DAY, GREGORY SCOTT · 2024 to 2025
$4.1MNIA NIH HHS K23 AG076960NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062677NIA NIH HHS R01 AG061111NIA NIH HHS R01 AG089380NIA NIH HHS R35 AG072362NIA NIH HHS R56 AG057195NIA NIH HHS R56 AG075744NIA NIH HHS U01 AG057195NIA NIH HHS U01 AG082350NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG032438NINDS NIH HHS R01 NS139383NINDS NIH HHS U01 NS120901
Abstract
Early-onset Alzheimer's disease (EOAD) and Late-onset AD (LOAD) differ in clinical presentations and rates of progression. We aimed to compare baseline and longitudinal tau PET burden, and their relationship with clinical variables in amyloid-PET positive, cognitively impaired participants from the Longitudinal Early-Onset Alzheimer's Disease Study (EOAD; n=390) and Alzheimer's Disease Neuroimaging Initiative (LOAD; n=211). Patients with EOAD showed higher baseline tau PET retention, broader neuroanatomical involvement and faster accumulation rates over time compared to LOAD, after adjusting for amyloid load and clinical stage. Tau PET showed stronger correlations with baseline amyloid burden and clinical measures of global cognition and function in EOAD than LOAD. We conclude that earlier age of onset in AD is linked to a more aggressive tauopathy, which in turn is a primary driver of clinical decline. These findings suggest that optimal therapeutic targets and strategies may differ between EOAD and LOAD.
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