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
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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). 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引用次数: 0
摘要
背景：以血液为基础对阿尔茨海默病（AD）进行疾病分期，有望发现可从疾病调整疗法中获益的个体。我们利用血浆生物标记物在淀粉样蛋白-β（Aβ）阳性个体中识别出 Braak V+（Braak V 和/或 VI）tau PET 阳性个体：在这项横断面研究中，我们对来自TRIAD队列的289人和来自WRAP研究的306人进行了AD连续性评估。我们用[18F]AZD4694或[11C]PiB进行了淀粉样蛋白PET评估，用[18F]MK6240进行了tau-PET评估，测量的血浆水平包括总tau、磷酸化tau异构体（pTau）pTau-181、pTau-217、pTau-231和N端tau（NTA-tau）。我们使用不同的分析平台评估了血浆生物标志物的性能，以预测Aβ+个体的Braak V+阳性率：在 TRIAD 中发现，血浆 pTau-217+Janssen （AUC [CI95%] = 0.97 [0.94, 1.0]）和 ALZpath pTau-217 （AUC [CI95%] = 0.93 [0.86, 1.0]）与 Aβ+ 患者 Braak V+ tau 阳性的关联度最高。在WRAP纵向研究中，血浆ALZpath pTau-217可区分出Braak V+ tau PET阳性个体（AUC [CI95%] = 0.97 [0.94, 1.0]）：因此，我们证明，使用调整后的临界值，血浆pTau-217可识别布拉克晚期tau累积的个体，这将有助于对患者进行分层治疗和临床研究：本研究得到了加拿大卫生研究院（CIHR）威斯顿脑研究所[MOP-11-51-31；RFN 152985、159815、162303]、加拿大神经变性与衰老联合会（CCNA；MOP-11-51-31 -team 1）、阿尔茨海默氏症协会（Alzheimer's Association）[NIRG-12-92090、NIRP-12-259245]、加拿大脑基金会（Brain Canada Foundation）（CFI Project 34874; 33397）、魁北克-圣地研究基金会（Fonds de Recherche du Québec-Santé, FRQS; Chercheur Boursier, 2020-VICO-279314）。P.R-N 和 SG 是 CIHR-CCNA 加拿大衰老神经退行性病变研究联合会的成员。Colin J. Adair 慈善基金会。
Identification of late-stage tau accumulation using plasma phospho-tau217.
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.
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