Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum

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• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Vilor Tejedor, Natàlia, 1988-
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author Sala Vila, Aleix
• dc.contributor.author Sánchez Benavides, Gonzalo
• dc.contributor.author Arenaza Urquijo, Eider M.
• dc.contributor.author Crous-Bou, Marta
• dc.contributor.author González de Echávarri, José Maria
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Simon, Maryline
• dc.contributor.author Kollmorgen, Gwendlyn
• dc.contributor.author Zetterberg, Henrik
• dc.contributor.author Blennow, Kaj
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author ALFA Study
• dc.date.accessioned 2020-10-13T05:59:23Z
• dc.date.available 2020-10-13T05:59:23Z
• dc.date.issued 2020
• dc.description.abstract Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid-β (Aβ)42, Aβ40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. Results: CSF t-tau, p-tau, and neurogranin increase throughout aging only in Aβ-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p-tau and p-tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.
• dc.description.sponsorship The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer's Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa‐17‐519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017‐SGR‐892. MSC received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska‐Curie action grant agreement No 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018‐037478‐I). JDG is supported by the Spanish Ministry of Science and Innovation (RYC‐2013‐13054). NVT is supported by the Spanish Ministry of Science, Innovation and Universities—Spanish State Research Agency (FJC2018‐038085‐I). OGR is supported by the Spanish Ministry of Science, Innovation and Universities (FJCI‐2017‐33437). ASV is the recipient of an Instituto de Salud Carlos III Miguel Servet II fellowship (CP II 17/00029). EMAU is supported by the Spanish Ministry of Science, Innovation and Universities—Spanish State Research Agency (RYC2018‐026053‐I). CM was supported by the Spanish Ministry of Economy and Competitiveness (grant n° IEDI‐2016‐00690). KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, and is supported by the Swedish Research Council (#2017‐00915); the Swedish Alzheimer Foundation (#AF‐742881), Hjärnfonden, Sweden (#FO2017‐0243); and a grant (#ALFGBG‐715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF‐agreement. HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council (#2018‐02532), the European Research Council (#681712), and a grant (#ALFGBG‐720931) from the Swedish state under the agreement between the Swedish government and the County Councils.
• dc.format.mimetype application/pdf
• dc.identifier.citation Milà-Alomà M, Salvadó G, Gispert JD, Vilor-Tejedor N, Grau-Rivera O, Sala-Vila A, Sánchez-Benavides G, Arenaza-Urquijo EM, Crous-Bou M, González-de-Echávarri JM, Minguillon C, Fauria K, Simon M, Kollmorgen G, Zetterberg H, Blennow K, Suárez-Calvet M, Molinuevo JL; ALFA study. Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum. Alzheimers Dement. 2020; 16(10):1358-71. DOI: 10.1002/alz.12131
• dc.identifier.doi http://dx.doi.org/10.1002/alz.12131
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/45463
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2020; 16(10):1358-71
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/752310
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681712
• dc.rights © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword Biomarker
• dc.subject.keyword Neurodegeneration
• dc.subject.keyword Neuroinflammation
• dc.subject.keyword Preclinical
• dc.title Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion