Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals

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• dc.contributor.author Martí Juan, Gerard
• dc.contributor.author Sanromà, Gerard
• dc.contributor.author Cacciaglia, Raffaele
• dc.contributor.author Falcón, Carles
• dc.contributor.author Operto, Grégory
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author González Ballester, Miguel Ángel, 1973-
• dc.contributor.author Domingo Gispert, Juan
• dc.contributor.author Piella Fenoy, Gemma
• dc.contributor.author Alzheimer’s Disease Neuroimaging Initiative
• dc.contributor.author ALFA Study
• dc.date.accessioned 2021-03-31T07:20:17Z
• dc.date.available 2021-03-31T07:20:17Z
• dc.date.issued 2020
• dc.description.abstract The ε4 allele of the gene Apolipoprotein E is the major genetic risk factor for Alzheimer's Disease. APOE ε4 has been associated with changes in brain structure in cognitively impaired and unimpaired subjects, including atrophy of the hippocampus, which is one of the brain structures that is early affected by AD. In this work we analyzed the impact of APOE ε4 gene dose and its association with age, on hippocampal shape assessed with multivariate surface analysis, in a ε4‐enriched cohort of n = 479 cognitively healthy individuals. Furthermore, we sought to replicate our findings on an independent dataset of n = 969 individuals covering the entire AD spectrum. We segmented the hippocampus of the subjects with a multi‐atlas‐based approach, obtaining high‐dimensional meshes that can be analyzed in a multivariate way. We analyzed the effects of different factors including APOE, sex, and age (in both cohorts) as well as clinical diagnosis on the local 3D hippocampal surface changes. We found specific regions on the hippocampal surface where the effect is modulated by significant APOE ε4 linear and quadratic interactions with age. We compared between APOE and diagnosis effects from both cohorts, finding similarities between APOE ε4 and AD effects on specific regions, and suggesting that age may modulate the effect of APOE ε4 and AD in a similar way.
• dc.description.sponsorship “la Caixa” Foundation, Grant/Award Number: LCF/PR/GN17/50300004; Ministry of Business and Knowledge of the Catalan Government, Grant/Award Number: 2017‐SGR‐892; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: MDM‐2015‐0502; Spanish Ministry of Science, Innovation and Universities, Grant/Award Number: RYC‐2013‐13054
• dc.format.mimetype application/pdf
• dc.identifier.citation Martí-Juan G, Sanroma-Guell G, Cacciaglia R, Falcon C, Operto G, Molinuevo JL, González Ballester MA, Domingo Gispert J, Piella G. Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals. Hum Brain Mapp. 2021;42(1):47-64. DOI: 10.1002/hbm.25202
• dc.identifier.doi http://dx.doi.org/10.1002/hbm.25202
• dc.identifier.issn 1065-9471
• dc.identifier.uri http://hdl.handle.net/10230/46998
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Human Brain Mapping. 2021;42(1):47-64
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/RYC2013-13054
• dc.rights © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License https://creativecommons.org/licenses/by-nc/4.0/ , which permits use, distribution and reproduction in anymedium, 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 https://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword APOE
• dc.subject.keyword Cognitively intact
• dc.subject.keyword Hippocampus
• dc.subject.keyword Multivariate analysis
• dc.title Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion