- December 27, 2025
- Agneta Nordberg, et al., Karolinska University
Topic/Product:
CNS Disease Panel 120
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma
Abstract
Understanding tau pathology progression across the Alzheimer’s disease (AD) continuum is critical for diagnosis and stratification. This study examined how age of onset and disease stage influence regional tau deposition using [¹⁸F]RO948-PET, and its relationship with plasma biomarkers, cognition, and cortical atrophy. In total, 57 participants underwent tau-PET, MRI, blood sampling, and neuropsychological testing: 39 patients with MCI (Aβ−/Aβ+) or AD, and 18 cognitively normal controls. The MCI Aβ+ and AD groups were further divided into early-onset (EOAD, <65y) and late-onset (LOAD, >65y) subgroups. MCI Aβ+ patients showed early tau accumulation in medial-temporal regions, extending to inferior-temporal cortex. MCI-EOAD exhibited more advanced neocortical tau binding, while MCI-LOAD showed intermediate lateral temporal involvement. In AD, EOAD patients had higher parietal tau burden than LOAD. Plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NFL) were elevated in MCI Aβ+ and AD. Plasma p-tau217 showed strong correlations with tau-PET in medial and inferior temporal regions, with weaker correlations in neocortical areas. EOAD showed non-linear tau-PET/p-tau217 associations, contrasting with LOAD’s linear pattern. Tau-PET was negatively correlated with global cognition and executive function, while p-tau217 better reflected early episodic memory decline. Both tau measures correlated with cortical thinning, especially in the entorhinal cortex. These findings highlight [¹⁸F]RO948-PET’s sensitivity in detecting early tau pathology and superiority in capturing individual differences in tau burden, particularly in advanced stages where plasma biomarkers plateaued. Tau-PET demonstrated superior resolution of disease progression and individual variability, reinforcing its value as a prognostic biomarker and a critical tool for patient stratification in clinical trials.
Authors & Affiliations
Mariola Zapater-Fajari¹†, Marco Bucci¹²†, Konstantinos Chiotis¹³, Ove Almkvist¹³, Anders Wall⁴⁵, Jonas Eriksson⁵⁶, Gunnar Antoni⁵⁶, Ilaria Pola⁷, Kübra Tan⁷, Wiebke Traichel⁷⁸, Andrea L. Benedet⁷, Nicholas J. Ashton⁷⁹¹⁰, Kaj Blennow⁷¹¹, Henrik Zetterberg⁷¹¹¹²¹³¹⁴¹⁵¹⁶, Nenad Bogdanovic¹³, and Agneta Nordberg¹³*
¹ Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
² Turku PET Center, Turku University Central Hospital, University of Turku and Åbo Akademi University, Turku, Finland
³ Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
⁴ Department of Surgical Sciences, Section of Molecular Imaging & Medical Physics, Uppsala University, Uppsala, Sweden
⁵ PET Centre, Uppsala University Hospital, Uppsala, Sweden
⁶ Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
⁸ Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
⁹ Institute of Psychiatry, Psychology & Neuroscience, King’s College London, Maurice Wohl Clinical Neuroscience Institute, London, UK
¹⁰ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia, South London and Maudsley NHS Foundation Trust, London, UK
¹¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
¹² Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
¹³ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
¹⁴ Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
¹⁵ Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
¹⁶ Centre for Brain Research, Indian Institute of Science, Bangalore, India
† These authors contributed equally to this work