Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome

Lleó, Alberto; Medrano-Martorell, Santiago; Fortea, Juan

Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome

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dc.contributor.author Lleó, Alberto
dc.contributor.author Medrano-Martorell, Santiago
dc.contributor.author Fortea, Juan
dc.date.accessioned 2022-06-23T06:34:15Z
dc.date.available 2022-06-23T06:34:15Z
dc.date.issued 2021
dc.description.abstract Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73-0.87] and 0.92 [95% CI 0.89-0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.
dc.description.sponsorship This study was supported by the Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III (PI14/01126 and PI17/01019 to J.F., PI13/01532 and PI16/01825 to R.B., PI18/00335 to M.C.I., PI18/00435 and INT19/00016 to D.A., PI15/01618 to R.R., PI14/1561 and AC19/00103 to A.L.) and the CIBERNED program (Program 1, Alzheimer Disease to A.L. and SIGNAL study, www.signalstudy.es), partly jointly funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. This work was also supported by the National Institutes of Health (NIA grants 1R01AG056850 - 01A1; R21AG056974 and R01AG061566 to J.F.), Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00408 to A.L.), Fundació La Marató de TV3 (20141210 to J.F., 044412 to R.B. and 201437.10 to R.R.); I. Illán-Gala is supported by the Rio Hortega grant (CM17/00074) from “Acción Estratégica en Salud 2013-2016” and the Global Brain Health Institute (https://www.gbhi.org/). Fundació Catalana Síndrome de Down and Fundació Víctor Grífols i Lucas partially supported this work. This work was also supported by Generalitat de Catalunya (SLT006/17/00119 to J.F., SLT006/17/95 to E.V. and SLT006/17/00125 to D.A.) and a grant from the Fundació Bancaria La Caixa to R.B. M.F.I. acknowledges support from the Jérôme Lejeune and Sysley D’Ornano Foundations. A Bejanin was the recipient of a Juan de la Cierva-Incorporación grant from the Spanish Ministry of Economy and Competitiveness (IJCI-2017-32609) and a Miguel Servet I grant (CP20/00038) from the Carlos III Health Institute. T.K.K. holds a research fellowship from the BrightFocus Foundation (#A2020812F) and is further supported by the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), 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. H.Z. 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 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), and the UK Dementia Research Institute at UCL. K.B. is supported by the Swedish Research Council (#2017-00915), 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), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). The authors would like to thank all the participants with Down’s syndrome, their families and their carers for their support of, and dedication to this research. We also acknowledge the Fundació Catalana Síndrome de Down for global support; Soraya Torres, Shaimaa El Bounasri, Laia Muñoz and Raúl Núñez for laboratory and sample handling; Reyes Alcoverro, Marta Salinas and Tania Martínez for administrative support; Concepción Escola for nursing handling. We also thank the clinicians for their help in acquiring the data reported in this article.
dc.format.mimetype application/pdf
dc.identifier.citation Lleó A, Zetterberg H, Pegueroles J, Karikari TK, Carmona-Iragui M, Ashton NJ et al. Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome. Nat Commun. 2021 Jul 14;12(1):4304. DOI: 10.1038/s41467-021-24319-x
dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-24319-x
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/53576
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2021 Jul 14;12(1):4304
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681712
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
dc.rights © The Author(s) 2021. 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.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 Predictive markers
dc.title Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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