Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study

Background: Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of...

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Autores: Vilor Tejedor, Natalia, Operto, Gregory, Evans, T. E., Falcon, Carles, Crous-Bou, Marta|||0000-0003-1493-4288, Minguillón, Carolina, Cacciaglia, Raffaele, Milà-Alomà, Marta, Grau-Rivera, Oriol|||0000-0002-4730-5341, Suárez-Calvet, Marc|||0000-0002-2993-569X, Garrido-Martín, Diego, Moran, S.|||0000-0003-4192-8983, Esteller, M.|||0000-0003-4490-6093, Adams, Hieab H. H.|||0000-0003-3687-2508, Molinuevo, José Luis|||0000-0003-0485-6001, Guigó, Roderic|||0000-0002-5738-4477, Gispert, Juan Domingo|||0000-0002-6155-0642
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:236585
Acceso en línea:https://ddd.uab.cat/record/236585
https://dx.doi.org/urn:doi:10.1007/s00429-020-02125-3
Access Level:acceso abierto
Palabra clave:APOE-ε4
BDNF
Hippocampal subfields
Imaging genetics
Subiculum
Val66Met
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spelling Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA studyVilor Tejedor, NataliaOperto, GregoryEvans, T. E.Falcon, CarlesCrous-Bou, Marta|||0000-0003-1493-4288Minguillón, CarolinaCacciaglia, RaffaeleMilà-Alomà, MartaGrau-Rivera, Oriol|||0000-0002-4730-5341Suárez-Calvet, Marc|||0000-0002-2993-569XGarrido-Martín, DiegoMoran, S.|||0000-0003-4192-8983Esteller, M.|||0000-0003-4490-6093Adams, Hieab H. H.|||0000-0003-3687-2508Molinuevo, José Luis|||0000-0003-0485-6001Guigó, Roderic|||0000-0002-5738-4477Gispert, Juan Domingo|||0000-0002-6155-0642APOE-ε4BDNFHippocampal subfieldsImaging geneticsSubiculumVal66MetBackground: Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whether there is an impact of BDNF Val66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-ε4 status. Methods: BDNF Val66Met and APOE genotypes were determined in a sample of 430 CU late/middle-aged participants from the ALFA study (ALzheimer and FAmilies). Participants underwent a brain 3D-T1-weighted MRI scan, and volumes of the HSv were determined using Freesurfer (v6.0). The effects of the BDNF Val66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-ε4 alleles and total intracranial volume. We also investigated whether the association between APOE-ε4 allele and HSv were modified by BDNF Val66Met genotypes. Results: BDNF Val66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated with APOE-ε4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-ε4 homozygous showed patterns of higher HSv than BDNF Val carriers. Conclusion: To our knowledge, the present study is the first to show that carrying the BDNF Val66Met polymorphisms partially compensates the decreased on HSv associated with APOE-ε4 in middle-age cognitively unimpaired individuals.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/236585https://dx.doi.org/urn:doi:10.1007/s00429-020-02125-3reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FJC2018-038085-IAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 SLT002-16-00201Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 IEDI-2016-00690European Commission https://doi.org/10.13039/501100000780 752310open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2365852026-06-06T12:50:31Z
dc.title.none.fl_str_mv Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
title Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
spellingShingle Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
Vilor Tejedor, Natalia
APOE-ε4
BDNF
Hippocampal subfields
Imaging genetics
Subiculum
Val66Met
title_short Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
title_full Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
title_fullStr Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
title_full_unstemmed Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
title_sort Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study
dc.creator.none.fl_str_mv Vilor Tejedor, Natalia
Operto, Gregory
Evans, T. E.
Falcon, Carles
Crous-Bou, Marta|||0000-0003-1493-4288
Minguillón, Carolina
Cacciaglia, Raffaele
Milà-Alomà, Marta
Grau-Rivera, Oriol|||0000-0002-4730-5341
Suárez-Calvet, Marc|||0000-0002-2993-569X
Garrido-Martín, Diego
Moran, S.|||0000-0003-4192-8983
Esteller, M.|||0000-0003-4490-6093
Adams, Hieab H. H.|||0000-0003-3687-2508
Molinuevo, José Luis|||0000-0003-0485-6001
Guigó, Roderic|||0000-0002-5738-4477
Gispert, Juan Domingo|||0000-0002-6155-0642
author Vilor Tejedor, Natalia
author_facet Vilor Tejedor, Natalia
Operto, Gregory
Evans, T. E.
Falcon, Carles
Crous-Bou, Marta|||0000-0003-1493-4288
Minguillón, Carolina
Cacciaglia, Raffaele
Milà-Alomà, Marta
Grau-Rivera, Oriol|||0000-0002-4730-5341
Suárez-Calvet, Marc|||0000-0002-2993-569X
Garrido-Martín, Diego
Moran, S.|||0000-0003-4192-8983
Esteller, M.|||0000-0003-4490-6093
Adams, Hieab H. H.|||0000-0003-3687-2508
Molinuevo, José Luis|||0000-0003-0485-6001
Guigó, Roderic|||0000-0002-5738-4477
Gispert, Juan Domingo|||0000-0002-6155-0642
author_role author
author2 Operto, Gregory
Evans, T. E.
Falcon, Carles
Crous-Bou, Marta|||0000-0003-1493-4288
Minguillón, Carolina
Cacciaglia, Raffaele
Milà-Alomà, Marta
Grau-Rivera, Oriol|||0000-0002-4730-5341
Suárez-Calvet, Marc|||0000-0002-2993-569X
Garrido-Martín, Diego
Moran, S.|||0000-0003-4192-8983
Esteller, M.|||0000-0003-4490-6093
Adams, Hieab H. H.|||0000-0003-3687-2508
Molinuevo, José Luis|||0000-0003-0485-6001
Guigó, Roderic|||0000-0002-5738-4477
Gispert, Juan Domingo|||0000-0002-6155-0642
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv APOE-ε4
BDNF
Hippocampal subfields
Imaging genetics
Subiculum
Val66Met
topic APOE-ε4
BDNF
Hippocampal subfields
Imaging genetics
Subiculum
Val66Met
description Background: Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whether there is an impact of BDNF Val66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-ε4 status. Methods: BDNF Val66Met and APOE genotypes were determined in a sample of 430 CU late/middle-aged participants from the ALFA study (ALzheimer and FAmilies). Participants underwent a brain 3D-T1-weighted MRI scan, and volumes of the HSv were determined using Freesurfer (v6.0). The effects of the BDNF Val66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-ε4 alleles and total intracranial volume. We also investigated whether the association between APOE-ε4 allele and HSv were modified by BDNF Val66Met genotypes. Results: BDNF Val66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated with APOE-ε4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-ε4 homozygous showed patterns of higher HSv than BDNF Val carriers. Conclusion: To our knowledge, the present study is the first to show that carrying the BDNF Val66Met polymorphisms partially compensates the decreased on HSv associated with APOE-ε4 in middle-age cognitively unimpaired individuals.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/236585
https://dx.doi.org/urn:doi:10.1007/s00429-020-02125-3
url https://ddd.uab.cat/record/236585
https://dx.doi.org/urn:doi:10.1007/s00429-020-02125-3
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FJC2018-038085-I
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 SLT002-16-00201
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 IEDI-2016-00690
European Commission https://doi.org/10.13039/501100000780 752310
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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