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ABSTRACT: Background
Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ?4 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-?4 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-?4 alleles and total intracranial volume. We also investigated whether the association between APOE-?4 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-?4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-?4 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-?4 in middle-age cognitively unimpaired individuals.
SUBMITTER: Vilor-Tejedor N
PROVIDER: S-EPMC7544723 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Vilor-Tejedor Natalia N Operto Grégory G Evans Tavia E TE Falcon Carles C Crous-Bou Marta M Minguillón Carolina C Cacciaglia Raffaele R Milà-Alomà Marta M Grau-Rivera Oriol O Suárez-Calvet Marc M Garrido-Martín Diego D Morán Sebastián S Esteller Manel M Adams Hieab H HH Molinuevo José Luis JL Guigó Roderic R Gispert Juan Domingo JD
Brain structure & function 20200817 8
<h4>Background</h4>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) ...[more]