Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts

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• dc.contributor.author Lantero Rodríguez, Juan
• dc.contributor.author Vrillon, Agathe
• dc.contributor.author Fernández-Lebrero, Aida
• dc.contributor.author Ortiz Romero, Paula, 1994-
• dc.contributor.author Snellman, Anniina
• dc.contributor.author Montoliu-Gaya, Laia
• dc.contributor.author Brum, Wagner S.
• dc.contributor.author Cognat, Emmanuel
• dc.contributor.author Dumurgier, Julien
• dc.contributor.author Puig-Pijoan, Albert
• dc.contributor.author Navalpotro-Gómez, Irene
• dc.contributor.author García-Escobar, Greta
• dc.contributor.author Karikari, Thomas K.
• dc.contributor.author Vanmechelen, Eugeen
• dc.contributor.author Ashton, Nicholas J.
• dc.contributor.author Zetterberg, Henrik
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Paquet, Claire
• dc.contributor.author Blennow, Kaj
• dc.date.accessioned 2024-03-18T08:22:43Z
• dc.date.available 2024-03-18T08:22:43Z
• dc.date.issued 2023
• dc.description.abstract Background Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer’s disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231. Methods CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n=212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n=175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ ). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ1–42/40 ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231). Results High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ− groups (Paris cohort: P ˂0.0001 for all; BIODEGMAR cohort: P ˂0.05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A−T− and A+T− groups (P ˂0.0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0.86 to 0.96) and discriminating AT groups (AUCs=0.79 to 0.98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts. Conclusions CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings.
• dc.description.sponsorship Open access funding provided by University of Gothenburg. This study was funded by the Swedish Research Council (#2017-00915 and #2022-00732), the Alzheimer Drug Discovery Foundation (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 National Institute of Health (NIH), USA, (grant #1R01AG068398-01). AV is supported by Fondation Ophtalmologique Adolphe de Rothschild and Fondation Vaincre Alzheimer. AES was supported by the Paulo Foundation, the Orion Research Foundation sr, and currently holds a postdoctoral fellowship from the Academy of Finland (#341059). TKK was funded by the Swedish Research Council (Vetenskapsrådet #2021-03244), the Alzheimer’s Association Research Fellowship (#AARF-21-850325), the Aina (Ann) Wallströms and Mary-Ann Sjöbloms stiftelsen and the Emil och Wera Cornells stiftelsen. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer 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 Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694) and the UK Dementia Research Institute at UCL (UKDRI-1003). MSC 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 Lantero-Rodriguez J, Vrillon A, Fernández-Lebrero A, Ortiz-Romero P, Snellman A, Montoliu-Gaya L, et al. Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts. Alzheimers Res Ther. 2023 Mar 10;15(1):48. DOI: 10.1186/s13195-023-01201-0
• dc.identifier.doi http://dx.doi.org/10.1186/s13195-023-01201-0
• dc.identifier.issn 1758-9193
• dc.identifier.uri http://hdl.handle.net/10230/59452
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Alzheimers Res Ther. 2023 Mar 10;15(1):48
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101053962
• 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 © The Author(s) 2023. 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• 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 CSF
• dc.subject.keyword Biomarkers
• dc.subject.keyword P-tau235
• dc.subject.keyword P-tau181
• dc.subject.keyword P-tau217
• dc.subject.keyword P-tau231
• dc.subject.keyword Memory clinic
• dc.title Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion