Plasma and CSF biomarkers in a memory clinic: head-to-head comparison of phosphorylated tau immunoassays

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• dc.contributor.author Ashton, Nicholas J.
• dc.contributor.author Puig Pijoan, Albert
• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Fernández-Lebrero, Aida
• dc.contributor.author Ortiz Romero, Paula, 1994-
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Navalpotro-Gómez, Irene
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author Manero, Rosa María
• dc.contributor.author Puente Periz, Victor Manuel
• dc.contributor.author Torre Fornell, Rafael de la
• dc.contributor.author Roquer, Jaume
• dc.contributor.author Suárez-Calvet, Marc
• dc.date.accessioned 2023-09-06T06:36:20Z
• dc.date.available 2023-09-06T06:36:20Z
• dc.date.issued 2023
• dc.description.abstract Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio. Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). Discussion: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. Highlights: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.
• dc.description.sponsorship The authors would like to express their most sincere gratitude to the BIODEGMAR participants and relatives without whom this research would have not been possible. The authors thank Anna Boronat Rigol, Rachael Burchfield, and Nicholas Kyle Proctor for technical support. They also thank all the staff at University of Gothenburg, Department of Neurology at Hospital del Mar, and Barcelonaβeta Brain Research Center, who supported this project. Thomas K. Karikari was funded by the Swedish Research Council (Vetenskåpradet), the Alzheimer's Association Research Fellowship (#AARF-21-850325), the BrightFocus Foundation (#A2020812F), the International Society for Neurochemistry's Career Development Grant, the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Swedish Parkinson Foundation (Parkinsonfonden), Gamla Tjänarinnor Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124), the Gun and Bertil Stohnes Foundation, and the Anna Lisa and Brother Björnsson's Foundation. Oriol Grau-Rivera is supported by the Spanish Ministry of Science, Innovation and Universities (IJC2020-043417-I), and receives funding from the Alzheimer's Association Research Fellowship Program (2019-AARF-644568) and the Instituto de Salud Carlos III (PI19/00117). Irene Navalpotro-Gómez receives funding from the Spanish Instituto de Salud Carlos III (ISCIII-FEDER, PI21/00194). Jaume Roquer receives funding from the Spanish Instituto de Salud Carlos III (ISCIII-FEDER, PI21/00194). Jeff L. Dage is supported by the National Institutes of Health (U24AG021886, P30AG072976, and U01AG057195), Roche Diagnostics (RD005665), as well as the Stark Neurosciences Research Institute at Indiana University School of Medicine. Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer's Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694), and the UK Dementia Research Institute at UCL. Kaj Blennow is supported by the Swedish Research Council (#2017-00915), ADDF, USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the NIH, USA (grant #1R01AG068398-01). Marc Suárez-Calvet receives funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 948677), Project “PI19/00155”, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and from a fellowship from “la Caixa” Foundation (ID 100010434) and from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847648 (LCF/BQ/PR21/11840004).
• dc.format.mimetype application/pdf
• dc.identifier.citation Ashton NJ, Puig-Pijoan A, Milà-Alomà M, Fernández-Lebrero A, García-Escobar G, González-Ortiz F, et al. Plasma and CSF biomarkers in a memory clinic: head-to-head comparison of phosphorylated tau immunoassays. Alzheimers Dement. 2023;19(5):1913–24. DOI: 10.1002/alz.12841
• dc.identifier.doi http://dx.doi.org/10.1002/alz.12841
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/57820
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2023;19(5):1913–24
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
• dc.rights © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Biomarker
• dc.subject.keyword Dementia
• dc.subject.keyword Disease
• dc.subject.keyword Phosphorylated tau
• dc.subject.keyword Plasma
• dc.subject.keyword Tau
• dc.title Plasma and CSF biomarkers in a memory clinic: head-to-head comparison of phosphorylated tau immunoassays
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion