The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer’s disease

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author González Ortiz, Fernando
• dc.contributor.author Vávra, Jakub
• dc.contributor.author Payne, Emma
• dc.contributor.author Kirsebom, Bjørn-Eivind
• dc.contributor.author Sjöbom, Ulrika
• dc.contributor.author Santos, Cristiano
• dc.contributor.author Júlvez Calvo, Jordi
• dc.contributor.author Kramer, Kaitlin
• dc.contributor.author Zalcberg, David
• dc.contributor.author Montoliu-Gaya, Laia
• dc.contributor.author Turton, Michael
• dc.contributor.author Harrison, Peter
• dc.contributor.author Hellström, Ann
• dc.contributor.author Zetterberg, Henrik
• dc.contributor.author Fladby, Tormod
• dc.contributor.author Sanders, Robert D.
• dc.contributor.author Blennow, Kaj
• dc.date.accessioned 2025-07-16T07:30:27Z
• dc.date.available 2025-07-16T07:30:27Z
• dc.date.issued 2025
• dc.description.abstract Tau phosphorylation plays an important role in brain physiology and pathology. During foetal development, it supports microtubule dynamics and neuroplasticity, whereas in Alzheimer’s disease (AD), it drives pathological tau aggregation and tangle formation. In this multicentre study (n = 462), we measured plasma phosphorylated-tau217 in healthy newborns, premature infants, patients with AD and healthy controls across various age groups. Plasma phosphorylated-tau217 levels were significantly higher in newborns compared to healthy individuals of any age group and even exceeded levels observed in patients with AD. In newborns, plasma phosphorylated-tau217 levels inversely correlated with perinatal factors such as gestational age. Longitudinal analysis of preterm infants demonstrated a decline in serum phosphorylated-tau217 levels over the first months of life, approaching levels observed in young adults. In contrast, elevated plasma phosphorylated-tau217 in older individuals was associated with AD pathology. Our findings corroborate the crucial role of tau phosphorylation in early brain development. However, in AD, tau phosphorylation transitions into a pathological mechanism. The high levels of blood-based phosphorylated-tau217 observed at birth and subsequent clearance might indicate distinct regulatory mechanisms that prevent tau aggregation in early life. Further studies are needed to explore the shared mechanisms of tau phosphorylation in newborns and AD.en
• dc.description.sponsorship K.B. is supported by the Swedish Research Council (#2017-00915 and #2022-00732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270 and #AF-994551), Hjärnfonden, Sweden (#ALZ2022-0006 and #FO2024-0048-TK-130), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-965240 and #ALFGBG-1006418), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), the Alzheimer’s Association 2022-2025 Grant (SG-23-1038904 QC), La Fondation Recherche Alzheimer (FRA), Paris, France, the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark and Familjen Rönströms Stiftelse, Stockholm, Sweden. The project was funded by the Norwegian Research Council, JPND/PMI-AD (NRC 311993), the National Institute of Health (R01 AG083874-01). F.G.-O. was funded by the Anna Lisa and Brother Björnsson’s Foundation and Emil och Maria Palms Foundation. M.S.-C. 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). B.-E.K. was supported by a grant from Helse-Nord (HNF1540-20). H.Z. is a Wallenberg scholar and a distinguished professor at the Swedish Research Council and receives funding from the Swedish Research Council (#2023-00356, #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement no. 101053962 and Swedish State Support for Clinical Research (#ALFGBG-71320).en
• dc.format.mimetype application/pdf
• dc.identifier.citation Gonzalez-Ortiz F, Vávra J, Payne E, Kirsebom BE, Sjöbom U, Santos C, et al. The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer’s disease. Brain Commun. 2025 Apr 30;7(3):1-11. DOI: 10.1093/braincomms/fcaf221
• dc.identifier.doi http://dx.doi.org/10.1093/braincomms/fcaf221
• dc.identifier.issn 2632-1297
• dc.identifier.uri http://hdl.handle.net/10230/70926
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Brain Communications. 2025 Apr 30;7(3):1-11
• 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/H2020/101053962
• dc.rights © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Phosphorylated tauen
• dc.subject.keyword Newbornsen
• dc.subject.keyword Plasma biomarkersen
• dc.subject.keyword Alzheimer’s diseaseen
• dc.title The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer’s diseaseen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion