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APOE-ε4 shapes the cerebral organization in cognitively intact individuals as reflected by structural gray matter networks

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dc.contributor.author Cacciaglia, Raffaele
dc.contributor.author Molinuevo, José Luis
dc.contributor.author Falcón, Carles
dc.contributor.author Arenaza Urquijo, Eider M.
dc.contributor.author Sánchez Benavides, Gonzalo
dc.contributor.author Brugulat Serrat, Anna, 1986-
dc.contributor.author Blennow, Kaj
dc.contributor.author Zetterberg, Henrik
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author ALFA Study
dc.date.accessioned 2021-05-05T07:33:09Z
dc.date.available 2021-05-05T07:33:09Z
dc.date.issued 2020
dc.identifier.citation Cacciaglia R, Molinuevo JL, Falcón C, Arenaza-Urquijo EM, Sánchez-Benavides G, Brugulat-Serrat A, et al. APOE-ε4 shapes the cerebral organization in cognitively intact individuals as reflected by structural gray matter networks. Cereb Cortex. 2020 Jun 1; 30(7): 4110-20. DOI: 10.1093/cercor/bhaa034
dc.identifier.issn 1047-3211
dc.identifier.uri http://hdl.handle.net/10230/47312
dc.description.abstract Gray matter networks (GMn) provide essential information on the intrinsic organization of the brain and appear to be disrupted in Alzheimer's disease (AD). Apolipoprotein E (APOE)-ε4 represents the major genetic risk factor for AD, yet the association between APOE-ε4 and GMn has remained unexplored. Here, we determine the impact of APOE-ε4 on GMn in a large sample of cognitively unimpaired individuals, which was enriched for the genetic risk of AD. We used independent component analysis to retrieve sources of structural covariance and analyzed APOE group differences within and between networks. Analyses were repeated in a subsample of amyloid-negative subjects. Compared with noncarriers and heterozygotes, APOE-ε4 homozygotes showed increased covariance in one network including primarily right-lateralized, parietal, inferior frontal, as well as inferior and middle temporal regions, which mirrored the formerly described AD-signature. This result was confirmed in a subsample of amyloid-negative individuals. APOE-ε4 carriers showed reduced covariance between two networks encompassing frontal and temporal regions, which constitute preferential target of amyloid deposition. Our data indicate that, in asymptomatic individuals, APOE-ε4 shapes the cerebral organization in a way that recapitulates focal morphometric alterations observed in AD patients, even in absence of amyloid pathology. This suggests that structural vulnerability in neuronal networks associated with APOE-ε4 may be an early event in AD pathogenesis, possibly upstream of amyloid deposition.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.rights Copyright © The Author(s) 2020. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title APOE-ε4 shapes the cerebral organization in cognitively intact individuals as reflected by structural gray matter networks
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/cercor/bhaa034
dc.subject.keyword APOE
dc.subject.keyword Alzheimer’s disease
dc.subject.keyword Gray matter networks
dc.subject.keyword Independent component analysis
dc.subject.keyword Processing speed
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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