EBioMedicine (Nov 2024)
Identification of late-stage tau accumulation using plasma phospho-tau217Research in context
- Marcel S. Woo,
- Joseph Therriault,
- Erin M. Jonaitis,
- Rachael Wilson,
- Rebecca E. Langhough,
- Nesrine Rahmouni,
- Andrea Lessa Benedet,
- Nicholas J. Ashton,
- Cécile Tissot,
- Juan Lantero-Rodriguez,
- Arthur C. Macedo,
- Stijn Servaes,
- Yi-Ting Wang,
- Jaime Fernandez Arias,
- Seyyed Ali Hosseini,
- Tobey J. Betthauser,
- Firoza Z. Lussier,
- Robert Hopewell,
- Gallen Triana-Baltzer,
- Hartmuth C. Kolb,
- Andreas Jeromin,
- Eliane Kobayashi,
- Gassan Massarweh,
- Manuel A. Friese,
- Jesse Klostranec,
- Paolo Vilali,
- Tharick A. Pascoal,
- Serge Gauthier,
- Henrik Zetterberg,
- Kaj Blennow,
- Sterling C. Johnson,
- Pedro Rosa-Neto
Affiliations
- Marcel S. Woo
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Centre Hamburg Eppendorf, 20251, Hamburg, Germany; Department of Neurology, University Medical Centre Hamburg Eppendorf, 20251, Hamburg, Germany; Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Corresponding author. Department of Neurology, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany.
- Joseph Therriault
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Erin M. Jonaitis
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA
- Rachael Wilson
- Wisconsin Alzheimer's Disease Research Centre, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53726, USA
- Rebecca E. Langhough
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA
- Nesrine Rahmouni
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada
- Andrea Lessa Benedet
- Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden
- Nicholas J. Ashton
- Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530, Gothenburg, Sweden
- Cécile Tissot
- Molecular Biophysics and Integrated Bioimaging Department, Lawrence Berkeley National Laboratory, Berkeley, 510, CA, USA
- Juan Lantero-Rodriguez
- Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden
- Arthur C. Macedo
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Stijn Servaes
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada
- Yi-Ting Wang
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Jaime Fernandez Arias
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada
- Seyyed Ali Hosseini
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada
- Tobey J. Betthauser
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA
- Firoza Z. Lussier
- Department of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA
- Robert Hopewell
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Gallen Triana-Baltzer
- Neuroscience Biomarkers, Johnson and Johnson Medical Innovation (formerly Janssen Research & Development), La Jolla, CA, 92121, USA
- Hartmuth C. Kolb
- Neuroscience Biomarkers, Johnson and Johnson Medical Innovation (formerly Janssen Research & Development), La Jolla, CA, 92121, USA
- Andreas Jeromin
- ALZpath. Inc, Carlsbad, CA, 92008, USA
- Eliane Kobayashi
- Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden
- Gassan Massarweh
- Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Manuel A. Friese
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Centre Hamburg Eppendorf, 20251, Hamburg, Germany
- Jesse Klostranec
- Montreal Neurologic Institute and Hospital, Department of Diagnostic and Interventional Neuroradiology, McGill University Health Centre, 3801 Rue University, Montréal, QC, H3A 2B4, Canada
- Paolo Vilali
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Tharick A. Pascoal
- Department of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA
- Serge Gauthier
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada
- Henrik Zetterberg
- Wisconsin Alzheimer's Disease Research Centre, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53726, USA; Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1E 6BT, UK; UK Dementia Research Institute at UCL, London, WC1E 6BT, UK; Hong Kong Centre for Neurodegenerative Diseases, Clear Water Bay, 518172 Hong Kong, China
- Kaj Blennow
- Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80, Mölndal, Sweden
- Sterling C. Johnson
- Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53726, USA; Wisconsin Alzheimer's Disease Research Centre, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53726, USA
- Pedro Rosa-Neto
- Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, QC H3A 1A1, Canada; Corresponding author. The McGill University Research Centre for Studies in Aging, 6875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada.
- Journal volume & issue
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Vol. 109
p. 105413
Abstract
Summary: Background: Blood-based disease staging across the Alzheimer's disease (AD) continuum holds the promise to identify individuals that profit from disease-modifying therapies. We set out to identify Braak V+ (Braak V and/or VI) tau PET-positive individuals within amyloid-β (Aβ)-positive individuals using plasma biomarkers. Methods: In this cross-sectional study, we assessed 289 individuals from the TRIAD cohort and 306 individuals from the WRAP study across the AD continuum. The participants were evaluated by amyloid-PET with [18F]AZD4694 or [11C]PiB and tau-PET with [18F]MK6240 and measured plasma levels included total tau, phospho-tau isoforms (pTau) pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers using different analytic platforms to predict Braak V+ positivity in Aβ+ individuals. Findings: Highest associations with Braak V+ tau positivity in Aβ+ individuals were found for plasma pTau-217+Janssen (AUC [CI95%] = 0.97 [0.94, 1.0]) and ALZpath pTau-217 (AUC [CI95%] = 0.93 [0.86, 1.0]) in TRIAD. Plasma ALZpath pTau-217 separated Braak V+ tau PET-positive individuals in the WRAP longitudinal study (AUC [CI95%] = 0.97 [0.94, 1.0]). Interpretation: Thus, we demonstrate that using adjusted cut-offs, plasma pTau-217 identifies individuals with later Braak stage tau accumulation which will be helpful to stratify patients for treatments and clinical studies. Funding: This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR) [MOP-11-51-31; RFN 152985, 159815, 162303], Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1), the Alzheimer's Association [NIRG-12-92090, NIRP-12-259245], Brain Canada Foundation (CFI Project 34874; 33397), the Fonds de Recherche du Québec—Santé (FRQS; Chercheur Boursier, 2020-VICO-279314). P.R-N and SG are members of the CIHR-CCNA Canadian Consortium of Neurodegeneration in Aging. Colin J. Adair Charitable Foundation.
