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
{"title":"Identification of late-stage tau accumulation using plasma phospho-tau217.","authors":"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","doi":"10.1016/j.ebiom.2024.105413","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sup>+</sup> (Braak V and/or VI) tau PET-positive individuals within amyloid-β (Aβ)-positive individuals using plasma biomarkers.</p><p><strong>Methods: </strong>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 [<sup>18</sup>F]AZD4694 or [<sup>11</sup>C]PiB and tau-PET with [<sup>18</sup>F]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<sup>+</sup> positivity in Aβ+ individuals.</p><p><strong>Findings: </strong>Highest associations with Braak V<sup>+</sup> tau positivity in Aβ+ individuals were found for plasma pTau-217+<sup>Janssen</sup> (AUC [CI<sub>95%</sub>] = 0.97 [0.94, 1.0]) and ALZpath pTau-217 (AUC [CI<sub>95%</sub>] = 0.93 [0.86, 1.0]) in TRIAD. Plasma ALZpath pTau-217 separated Braak V<sup>+</sup> tau PET-positive individuals in the WRAP longitudinal study (AUC [CI<sub>95%</sub>] = 0.97 [0.94, 1.0]).</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>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.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2024.105413","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍:
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.