Welcome to the UPF Digital Repository

Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease

Show simple item record

dc.contributor.author Milà Alomà, Marta
dc.contributor.author Shekari, Mahnaz
dc.contributor.author Salvadó, Gemma
dc.contributor.author Ortiz Romero, Paula, 1994-
dc.contributor.author González-Escalante, Armand
dc.contributor.author Sánchez Benavides, Gonzalo
dc.contributor.author Minguillón, Carolina
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author Suárez-Calvet, Marc
dc.contributor.author Blennow, Kaj
dc.date.accessioned 2023-02-09T08:07:20Z
dc.date.available 2023-02-09T08:07:20Z
dc.date.issued 2022
dc.identifier.citation Milà-Alomà M, Ashton NJ, Shekari M, Salvadó G, Ortiz-Romero P, Montoliu-Gaya L, et al. Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease. Nat Med. 2022 Sep;28(9):1797-801. DOI: 10.1038/s41591-022-01925-w
dc.identifier.issn 1078-8956
dc.identifier.uri http://hdl.handle.net/10230/55683
dc.description.abstract Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer's disease clinical trials.
dc.description.sponsorship The research leading to these results received funding from ‘la Caixa’ Foundation (ID 100010434), under agreement LCF/PR/GN17/10300004 and the Alzheimer’s Association, and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). E.V. was supported by Flanders Innovation and Entrepreneurship (VLAIO grant no. 140105). C.M. received funding within the context of EURO-FINGERS, a EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The EURO-FINGERS project is supported through the following funding organizations under the aegis of JPND—www.jpnd.eu: Finland: Academy of Finland; Germany: Federal Ministry of Education and Research; Spain: National Institute of Health Carlos III; Luxembourg: National Research Fund; Hungary: National Research, Development and Innovation Office; and The Netherlands: Netherlands Organisation for Health Research and Development (ZonMW-Memorabel no. 733051102). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (grant no. 2018-02532), the European Research Council (ERC, grant no. 681712), Swedish State Support for Clinical Research (grant no. ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (grant no. 201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (grant nos. 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 (grant no. FO2019-0228), the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 860197 (MIRIADE) and the UK Dementia Research Institute at University College London (UCL). J.D.G. is supported by the Spanish Ministry of Economy and Competitiveness (RYC-2013-13054) and received research support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking AMYPAD (grant no. 115952) and from Ministerio de Ciencia, Innovación y Universidades (grant no. RTI2018-102261). M.S.C. receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 948677), the Instituto de Salud Carlos III (PI19/00155), and from the ERC under the EU’s ‘la Caixa’ Foundation (ID 100010434) and from the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant (no. 847648, LCF/BQ/PR21/11840004). K.B. is supported by the Swedish Research Council (grant no. 2017-00915), the ADDF, USA (grant no. RDAPB-201809-2016615), the Swedish Alzheimer Foundation (grant no. AF-742881) (grant nos. AF-930351, AF-939721 and AF-968270), Hjärnfonden, Sweden (grant nos. FO2017-0243 and ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF agreement (grant nos. ALFGBG-715986 and ALFGBG-965240), the EU Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the National Institutes of Health (grant no. 1R01AG068398-01) and the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Med. 2022 Sep;28(9):1797-801
dc.rights © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41591-022-01925-w
dc.subject.keyword Alzheimer's disease
dc.subject.keyword Predictive markers
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681712
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.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking