The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals

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• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Operto, Grégory
• dc.contributor.author Cumplido-Mayoral, Irene
• dc.contributor.author Arenaza Urquijo, Eider M.
• dc.contributor.author Cacciaglia, Raffaele
• dc.contributor.author Falcón, Carles
• dc.contributor.author Vilor Tejedor, Natàlia, 1988-
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author ADNI
• dc.date.accessioned 2022-03-24T06:57:57Z
• dc.date.available 2022-03-24T06:57:57Z
• dc.date.issued 2022
• dc.description.abstract Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
• dc.description.sponsorship The project leading to this study has received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN17/50300004. Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant number 2017-SGR-892. EMAU is supported by the Spanish Ministry of Science, Innovation and Universities–Spanish State Research Agency (RYC2018-026053-I).
• dc.format.mimetype application/pdf
• dc.identifier.citation Salvadó G, Ferreira D, Operto G, Cumplido-Mayoral I, Arenaza-Urquijo EM, Cacciaglia R et al. The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals. Alzheimers Dement. 2022;18(7):1383-95. DOI: 10.1002/alz.12487
• dc.identifier.doi http://dx.doi.org/10.1002/alz.12487
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/52764
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2022;18(7):1383-95
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RYC2018-026053-I
• 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 (http://creativecommons.org/licenses/by-nc/4.0/), 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's disease
• dc.subject.keyword Alzheimer's disease signature
• dc.subject.keyword Apolipoprotein E ε2 carrier
• dc.subject.keyword Brain maintenance
• dc.subject.keyword Brain morphology
• dc.subject.keyword Brain reserve
• dc.subject.keyword Cognitive reserve
• dc.subject.keyword Magnetic resonance
• dc.subject.keyword Multi-site
• dc.subject.keyword Resilience signature
• dc.title The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion