Cerebral amyloid-β load is associated with neurodegeneration and gliosis: Mediation by p-tau and interactions with risk factors early in the Alzheimer's continuum

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• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Shekari, Mahnaz
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Niñerola-Baizán, Aida
• dc.contributor.author Perissinotti, Andrés
• dc.contributor.author Kollmorgen, Gwendlyn
• dc.contributor.author Buckley, Christopher, 1948-
• dc.contributor.author Farrar, Gill
• 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 Gispert López, Juan Domingo
• dc.contributor.author ALFA Study
• dc.date.accessioned 2021-04-19T07:32:55Z
• dc.date.available 2021-04-19T07:32:55Z
• dc.date.issued 2021
• dc.description.abstract Introduction: The association between cerebral amyloid-β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. Methods: In 318 cognitively unimpaired participants, we assessed the association between amyloid-β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE-ε4), and the mediation effect of tau and neurodegeneration were also investigated. Results: Centiloids were positively associated with CSF biomarkers of tau pathology (p-tau), neurodegeneration (t-tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL-40, GFAP, sTREM2), presenting interactions with age (p-tau, t-tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p-tau, except for NfL. The interaction between sex and amyloid-β on sTREM2 and NfL was also tau-independent. Discussion: Early amyloid-β accumulation has a tau-independent effect on neurodegeneration and a tau-dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.
• dc.format.mimetype application/pdf
• dc.identifier.citation Salvadó G, Milà-Alomà M, Shekari M, Minguillon C, Fauria K, Niñerola-Baizán A, Perissinotti A, Kollmorgen G, Buckley C, Farrar G, Zetterberg H, Blennow K, Suárez-Calvet M, Molinuevo JL, Gispert JD; ALFA study. Cerebral amyloid-β load is associated with neurodegeneration and gliosis: Mediation by p-tau and interactions with risk factors early in the Alzheimer's continuum. Alzheimers Dement. 2021;17(5):788-800. DOI: 10.1002/alz.12245
• dc.identifier.doi http://dx.doi.org/10.1002/alz.12245
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/47145
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2021;17(5):788-800.
• dc.rights © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Alzheimer
• dc.subject.keyword [18F]flutemetamol
• dc.subject.keyword Biomarkers
• dc.subject.keyword Glial activation
• dc.subject.keyword Inflammation
• dc.subject.keyword Modulation
• dc.subject.keyword Neuronal injury
• dc.subject.keyword Preclinical
• dc.title Cerebral amyloid-β load is associated with neurodegeneration and gliosis: Mediation by p-tau and interactions with risk factors early in the Alzheimer's continuum
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion