Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts

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• dc.contributor.author Cacciaglia, Raffaele
• dc.contributor.author Falcón, Carles
• dc.contributor.author Sánchez Benavides, Gonzalo
• dc.contributor.author Brugulat Serrat, Anna, 1986-
• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author Fauria, Karine
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Kollmorgen, Gwendlyn
• dc.contributor.author Quijano Rubio, Clara
• dc.contributor.author Blennow, Kaj
• dc.contributor.author Zetterberg, Henrik
• dc.contributor.author Lorenzini, Luigi
• dc.contributor.author Wink, Alle Meije
• dc.contributor.author Ingala, Silvia
• dc.contributor.author Barkhof, Frederik
• dc.contributor.author Ritchie, Craig
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author ALFA Study
• dc.date.accessioned 2025-10-03T06:20:35Z
• dc.date.available 2025-10-03T06:20:35Z
• dc.date.issued 2025
• dc.description.abstract Introduction: Identifying the link between early Alzheimer's disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals. Methods: We used longitudinal voxel-based morphometry (VBM) in combination with hippocampal subfield segmentation. Changes in neuroimaging and cognitive variables were inspected using general linear models (GLMs) adjusting by age, sex, apolipoprotein E (APOE) status, follow-up time, and years of education. Results: In both cohorts, baseline CSF amyloid beta (Aβ) biomarkers significantly predicted medial temporal lobe (MTL) atrophy rates and episodic memory (EM) decline independently of CSF phosphorylated tau (p-tau). Discussion: Our data suggest that soluble Aβ dyshomeostasis triggers MTL longitudinal atrophy and EM decline independently of CSF p-tau. Our data underscore the need for secondary preventive strategies at the earliest stages of the AD pathological cascade. Highlights: We assessed brain atrophy and cognitive decline in asymptomatic individuals. Aβ biomarkers predicted MTL atrophy independently of p-tau. Our results underscore the importance of undertaking Alzheimer's preclinical trials.
• dc.description.sponsorship The research 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. 2021 SGR 00913. RC receives funding from MCIN/AEI/10.13039/501100011033/FEDER, EU, through project PID2021-125433OA-100, and support from grant RYC2021-031128-I, funded by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cacciaglia R, Falcón C, Benavides GS, Brugulat-Serrat A, Alomà MM, Calvet MS, et al. Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts. Alzheimers Dement. 2025 Feb;21(2):e14415. DOI: 10.1002/alz.14415
• dc.identifier.doi http://dx.doi.org/10.1002/alz.14415
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/71350
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2025 Feb;21(2):e14415
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-125433OA-100
• dc.rights © 2025 The Author(s). 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 License (http://creativecommons.org/licenses/by/4.0/), which permits use, 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 Amyloid beta
• dc.subject.keyword Cerebrospinal fluid
• dc.subject.keyword Medial temporal lobe
• dc.subject.keyword Memory
• dc.subject.keyword p‐tau
• dc.title Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion