Plasma phospho-tau217 for Alzheimer's disease diagnosis in primary and secondary care using a fully automated platform

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• dc.contributor.author Palmqvist, Sebastian
• dc.contributor.author Anastasi, Federica
• dc.contributor.author Puig-Pijoan, Albert
• dc.contributor.author Fernández-Lebrero, Aida
• dc.contributor.author Contador, Jose
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Hansson, Oskar
• dc.date.accessioned 2025-09-04T14:53:16Z
• dc.date.available 2025-09-04T14:53:16Z
• dc.date.issued 2025
• dc.description.abstract Global implementation of blood tests for Alzheimer's disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, n = 337), Gothenburg (Sweden, n = 165), Barcelona (Spain, n = 487) and Brescia (Italy, n = 230), and a primary care cohort in Sweden (n = 548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93-0.96. In secondary care, the accuracies were 89-91%, the positive predictive values 89-95% and the negative predictive values 77-90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, APOE genotype or cognitive stage. Using a two-cutoff approach, accuracies increased to 92-94% in secondary and primary care, excluding 12-17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing mass-spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age. In conclusion, this fully automated p-tau217 test demonstrates high accuracy for identifying AD pathology. A two-cutoff approach might be necessary to optimize performance across diverse settings and subpopulations.
• dc.description.sponsorship We would like to express our gratitude to the participants, and relatives, in all studies, without whom this research would have not been possible. In addition, we thank B. Arslan for analyzing plasma Aβ in the Gothenburg cohort. The BioFINDER group was supported by the National Institute of Aging (grant no. R01AG083740 to O.H., S.P., R.O. and S.J.), Alzheimer’s Association (grant nos. SG-23-1061717 and ZEN24-1069572 to O.H.), GHR Foundation (O.H. and S.P.), European Research Council (ERC, grant no. ADG-101096455 to O.H.), Swedish Research Council (grant nos. 2023-00356 to O.H., 2021-02219 to N.M.-C. and 2018-02052 to S.P.), ERA PerMed (grant no. ERAPERMED2021-184 to O.H.), the Knut and Alice Wallenberg Foundation (grant no. 2022-0231 to O.H.), the European Union’s (EU’s) Horizon Europe research and innovation program under grant agreement no. 101053962 (to O.H.), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University (to O.H.), the Swedish Alzheimer Foundation (grant nos. AF-1011949 and AF-994075 to S.P., AF-994229 to N.M.-C. and AF-981132 to S.P.), the Swedish Brain Foundation (grant nos. FO2023-0163 to N.M.-C., FO2024-0284 and FO2022-0204 to S.P. and FO2021-0293 to O.H.), the family Rönström’s Foundation (grant nos. FRS-0003 to N.M.-C. and FRS-0004 and FRS-0011 to S.P.), the Berg Family Foundation (O.H.), the Parkinson Foundation of Sweden (grant no. 1412/22 to O.H.), the Cure Alzheimer’s fund (O.H.), the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (O.H.), the Skåne University Hospital Foundation (grant no. 2020-O000028 to S.P.), EU Joint Programme Neurodegenerative Diseases (grant no. 2019-03401 to N.M.-C.), WASP and DDLS Joint call for research projects (grant no. WASP/DDLS22-066 to N.M.-C.), Regionalt Forskningsstöd (grant no. 2022-1346 to S.P.) and the Swedish Federal Government under the ALF-agreement (grant nos. 2022-Projekt0107 to N.M.-C., 2022-Projekt0080 to O.H. and 2018-Projekt0226 to S.P.). The precursor of [18F]flutemetamol was sponsored by GE Healthcare. For the Gothenburg group, S.K. was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (nos. ALFGBG-1005471, ALFGBG-965923, ALFGBG-81392 and ALFGBG-771071), the Alzheimerfonden (grant nos. AF-842471, AF-737641, AF-929959 and AF-939825), the Swedish Research Council (grant nos. 2019-02075 and 2019-02075_15), Stiftelsen Psykiatriska Forskningsfonden and the Swedish Brain Foundation (grant no. FO2024-0097). A.D. was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (grant no. ALFGBG-984092). H.Z. is a Wallenberg Scholar and a distinguished professor at the Swedish Research Council. K.B. is supported by the Swedish Research Council (grant nos. 2017-00915 and 2022-00732), the Swedish Alzheimer Foundation (grant nos. AF-930351, AF-939721, AF-968270 and AF-994551), Hjärnfonden, Sweden (grant nos. ALZ2022-0006, FO2024-0048-TK-130 and FO2024-0048-HK-24), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (grant nos. ALFGBG-965240 and ALFGBG-1006418), the Alzheimer’s Association 2022–2025 (grant no. SG-23-1038904 QC), the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark, Familjen Rönströms Stiftelse, Stockholm, Sweden and an anonymous philanthropist and donor. The Barcelona group thanks P. Ortiz-Romero, M. de Diego, E. Jiménez, J. Torres and M. del Campo for technical support. F.A. received funding from grant no. JDC2022-049347-I, funded by the MCIU/AEI/10.13039/501100011033 and the EU NextGeneration EU/PRTR. M.S.-C. received funding from the ERC under the EU’s Horizon 2020 research and innovation program (grant no. 948677); ERA PerMed-ERA NET and the Generalitat de Catalunya (Departament de Salut) through project no. SLD077/21/000001; project PI19/00155 and PI22/00456, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the EU; and from a fellowship from ‘la Caixa’ Foundation (ID 100010434) and the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant no. 847648 (LCF/BQ/PR21/11840004)). For the Brescia group, A. Pilotto has beensupported by grants of Airalzh Foundation AGYR2021) Life-BIO grant, the LIMPE-DISMOV Foundation Segala Grant 2021, the Italian Ministry of University and Research PRIN COCOON (2017MYJ5TH) and PRIN 2021 RePlast (20202THZAW), the H2020 IMI IDEA-FAST (ID853981) and the Italian Ministry of Health, grant/award nos. RF-2018-12366209 and PNRR-Health PNRR-MAD-2022-12376110. V.Q. was supported by the H2020 IMI IDEA-FAST (grant no. ID853981). C.T. was supported by the PRIN 2021 RePlast (grant no. 20202THZAW). A. Padovani has been supported by grants of the Italian Ministry of University and Research PRIN COCOON (2017MYJ5TH) and PRIN 2021 RePlast (20202THZAW), the H2020 IMI IDEA-FAST (ID853981) and the Italian Ministry of Health, grant/award nos. RF-2018-12366209, RF-2019 RF-2019-12369272 and PNRR-Health PNRR-MAD-2022-12376110. The funders had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review or approval of the paper and decision to submit the paper for publication.
• dc.format.mimetype application/pdf
• dc.identifier.citation Palmqvist S, Warmenhoven N, Anastasi F, Pilotto A, Janelidze S, Tideman P, et al. Plasma phospho-tau217 for Alzheimer's disease diagnosis in primary and secondary care using a fully automated platform. Nat Med. 2025 Jun;31(6):2036-43. DOI: 10.1038/s41591-025-03622-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41591-025-03622-w
• dc.identifier.issn 1078-8956
• dc.identifier.uri http://hdl.handle.net/10230/71115
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Med. 2025 Jun;31(6):2036-43
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101053962
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/853981
• dc.rights © The Author(s) 2025. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword Diagnostic markers
• dc.title Plasma phospho-tau217 for Alzheimer's disease diagnosis in primary and secondary care using a fully automated platform
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion