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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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