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Publications

Journal Article Ahead of print

PubMed: 42360329 DOI: 10.1007/s00259-026-08015-w

[ 18F]RO948 Tau PET in early and late onset Alzheimer's disease: associations with plasma p-tau 217, atrophy and cognition.

Eur J Nucl Med Mol Imaging

Authors: Mariola Zapater-Fajari, Marco Bucci, Konstantinos Chiotis, Ove Almkvist, Anders Wall, Jonas Eriksson, Gunnar Antoni, Ilaria Pola, Kübra Tan, Wiebke Traichel, Andrea L Benedet, Nicholas J Ashton, Henrik Zetterberg, Nenad Bogdanovic, Agneta Nordberg

Affiliations

  • Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Neo 7th Floor, Stockholm, 14183, Sweden.
  • Turku PET Center, Turku University Central Hospital, University of Turku and Åbo Akademi University, Turku, 20251, Finland.
  • Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Department of Surgical Sciences, Section of Molecular Imaging & Medical Physics, Uppsala University, Uppsala, 75185, Sweden.
  • PET Centre, Uppsala University Hospital, Uppsala, 75185, Sweden.
  • Department of Medicinal Chemistry, Uppsala University, Uppsala, 75123, Sweden.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
  • Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Frederik V's Vej 11, 3, Copenhagen, 2100, Denmark.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden. Institute of Psychiatry, Psychology & Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, SE5 9RT, UK. NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, SE5 8AF, UK.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, 43180, Sweden. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK. Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, 999077, China. Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, 53792-2420, USA. Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, 53792-2420, USA. Centre for Brain Research, Indian Institute of Science, C.V. Raman Avenue, Bangalore, 560 012, India.
  • Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Neo 7th Floor, Stockholm, 14183, Sweden.
  • Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, 14186, Sweden.

Abstract

PURPOSE

The aim of this study was to compare regional brain tau extent across the disease spectrum in early- and late-onset Alzheimer's disease using the second-generation tau PET tracer [ 18F]RO948, and to investigate the relationship between PET-derived patterns, plasma p-tau217, brain atrophy, and cognition.

METHODS

We examined 57 participants: 39 patients from the Cognitive Assessment Unit at Karolinska University Hospital (Stockholm/Sweden)-diagnosed as MCI Aβ- (n = 10), MCI Aβ + (n = 16; 8 EO and 6 LO), and AD (n = 13; 5 EOAD and 8 LOAD)-and 18 cognitively normal controls. All participants underwent [ 18F]RO948 tau-PET, structural MRI, cognitive testing, and plasma p-tau217 analysis.

RESULTS

Both EO and LO MCI (Aß +) showed higher [ 18F]RO948 binding in amygdala, entorhinal cortex, hippocampus (p < 0.001) and extending to inferior temporal regions (p < 0.01) compared to controls, with some MCI-EO cases already showing advanced neocortical tau burden. At the AD stage, EOAD patients showed greater neocortical tau extent in temporo-parietal and frontal cortices than LOAD. P‑tau217 positively correlated with [ 18F]RO948 in amygdala, entorhinal cortex, hippocampus (rho = 0.81) followed by temporal (rho = 0.71), and parietal cortices (rho = 0.56, all p < 0.001). The Tau‑PET/p-tau217 association was different between EOAD and LOAD with greater differences in parietal cortices. Tau‑PET also showed stronger region‑specific associations with cognitive impairment than p‑tau217, especially in EOAD.

CONCLUSIONS

[ 18F]RO948-PET captured interindividual heterogeneity in tau accumulation that was not reflected by plasma p-tau217. This dissociation was particularly evident in neocortical regions, where LOAD showed elevated plasma p-tau217 levels despite low tau PET binding. These findings highlight the value of tau-PET as a sensitive biomarker for detecting early disease heterogeneity, assessing disease severity, and improving patient stratification for disease-modifying treatments.

MeSH

Hippocampus, Entorhinal Cortex, Atrophy, Alzheimer Disease, Brain, Amygdala, Parietal Lobe, Cognition, Plasma