Tau, a protein that forms abnormal deposits in Alzheimer's disease, accumulates more than twice as fast and more widely in younger patients than in older patients. A new study published in Science Translational Medicine by researchers at Karolinska Institutet and the University of California, San Francisco shows this. The findings highlight the importance of earlier diagnosis and access to advanced brain imaging.
The largest comparison of tau pathology in early- and late-onset Alzheimer's included 390 participants whose symptoms began before age 65 and 211 with later-onset disease.
Tau PET scans, which reveal the amount and location of abnormal tau deposits, showed more extensive pathology in younger patients, even when symptoms were mild. Repeat scans over two to three years also showed faster accumulation.
"Younger patients had substantially more tau even after accounting for differences in clinical severity. Their tau also accumulated faster over time. Delayed diagnosis alone does not explain this pattern", says Konstantinos Chiotis , assistant professor at the Department of Neurobiology, Care Sciences and Society , Karolinska Institutet and neurologist at Karolinska University Hospital and first author of the study.
Recognising symptoms beyond memory loss
In later-onset Alzheimer's, early concerns often involve repeating questions or forgetting appointments. Younger patients commonly have memory problems too, but difficulties planning, organising and managing tasks involving several steps can be particularly prominent.
Patients or families may describe increasing difficulty managing work or family responsibilities, sometimes alongside social withdrawal. These changes can be mistaken for depression or burnout. Around one in five younger participants had a presentation dominated by symptoms other than memory loss, such as difficulty finding words, reading or interpreting visual information.
The findings reinforce the importance of assessing language, visual and spatial abilities, and executive function alongside memory, with attention to changes from previous abilities. Research on young-onset dementia has reported diagnostic delays around one to two years longer than in older patients.
Earlier diagnosis and access to tau PET
Delayed recognition during working life can affect employment, financial security and family responsibilities, while postponing care and support. Healthcare priorities and diagnostic pathways need to reflect these patients' needs.
"We need greater awareness of Alzheimer's in younger adults and better access to specialist assessment, including tau PET when clinically appropriate. These scans show how much tau pathology is present and where it is located, helping us understand unusual symptoms and how far the disease has progressed biologically," says Konstantinos Chiotis.
Implications for treatment
Current disease-modifying treatments target amyloid, another protein involved in Alzheimer's. In Sweden, lecanemab is offered through private care, while national recommendations advise against its use in publicly funded healthcare.
Differences between younger and older patients were much greater for tau and remained after accounting for amyloid levels. Treatment studies suggest that existing tau burden may influence the benefit of amyloid-lowering therapies.
"We do not yet know whether younger patients benefit differently. But finding extensive tau even when symptoms are mild makes timely diagnosis especially important. We need to identify patients early enough to give treatments the best opportunity to help," says Konstantinos Chiotis.
Funding included the US National Institute on Aging (NIH) and the Alzheimer's Association, with KI faculty support for Konstantinos Chiotis' assistant professorship.
Publication
Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer's disease ,
K. Chiotis, G. Blazhenets, D. N. Soleimani-Meigooni, P. S. Aisen, A. Amuiri, A. Atri, L. Beckett, M. Brickhouse, D. G. Clark, J. L. Dage, G. S. Day, R. Duara, A. Eloyan, T. Foroud, N. R. Graff-Radford, I. M. Grant, D. B. Hammers, L. S. Honig, E. C. B. Johnson, D. T. Jones, K. Kirby, R. Koeppe, J. H. Kramer, W. A. Kukull, J. Lagarde, A. Leuzy, P. Maiti, J. C. Masdeu, M. F. Mendez, E. Musiek, K. N. Nudelman, C. U. Onyike, M. Riddle, S. Rocha, E. Rogalski, S. Salloway, D. R. Schonhaut, S. Sha, R. Shankar, A. Taurone, M. Thangarajah, A. W. Toga, A. Touroutoglou, R. Scott Turner, P. Vemuri, T. S. Wingo, D. A. Wolk, K. Womack, J. Zhang, M. C. Carrillo, B. C. Dickerson, L. G. Apostolova, R. La Joie, G. D. Rabinovici, the Longitudinal Early-onset Alzheimer's Disease Study consortium and the Alzheimer's Disease Neuroimaging Initiative,
Science Translational Medicine, 4 November 2026. Doi:10.64898/2026.01.25.26344738
