Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer’s disease

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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Publication Details

Journal
medRxiv
Published
2026-01-26
DOI
https://doi.org/10.64898/2026.01.25.26344738
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer’s disease

Michael Brickhouse, Ganna Blazhenets, Ani Eloyan, Alinda Amuiri et al.
medRxiv
Dementia and Cognitive Impairment Research
article

Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer’s disease

Michael Brickhouse, Ganna Blazhenets, Ani Eloyan, Alinda Amuiri, Kala Kirby, D. Richard Jones, Gregory S Day, Ranjan Duara, Jeffrey L Dage, Robert Koeppe, Bradford C Dickerson, Lawrence S Honig, Tatiana Foroud, Neill R Graff-Radford, Joel H Kramer, Paul S Aisen, Laurel Beckett, David G Clark, Walter A Kukull, David N Soleimani-Meigooni, Alireza Atri, Erik C. B. Johnson, Ian M Grant, Konstantinos Chiotis, Dustin B Hammers
article en

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.

medRxiv
Northwestern University (US), Alzheimer's Association (US), Houston Methodist (US), Rhode Island Department of Health (US), Mayo Clinic (US), Johns Hopkins University (US), Emory University (US), University of California, Los Angeles (US), Palo Alto University (US), University of California, San Francisco (US), Georgetown University (US), University of Washington (US), Washington University in St. Louis (US), Cornell University (US), Brown University (US), University of Michigan (US), Columbia University Irving Medical Center (US), Johns Hopkins Medicine (US), Keck Hospital of USC (US), Jacksonville College (US), Banner Health (US), Karolinska Institutet (SE), Massachusetts General Hospital (US), Mount Sinai Medical Center (US), Behavioral Pharma (United States) (US), University Memory and Aging Center (US), Methodist Hospital (US), Michigan Medicine (US), Wallenberg Wood Science Center (SE), Mayo Clinic in Arizona (US), University of Washington Applied Physics Laboratory (US), Banner Sun Health Research Institute (US), Mayo Clinic in Florida (US), Indiana University – Purdue University Indianapolis (US), University of San Francisco (US), University of Pennsylvania (US), University of California, Davis (US), University of Gothenburg (SE), Southern States University (US), Stanford University (US)
Foundation for the National Institutes of Health, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, Meso Scale Diagnostics, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, Fondation pour la Recherche sur Alzheimer, National Institutes of Health, Genentech, University of California, San Francisco, Avid Radiopharmaceuticals, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Neurological Disorders and Stroke
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