Suchergebnisse

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. ; The research leading to these results has received funding from "la Caixa" Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016–2020 grant# SLT002/16/00201). CM was supported by the Spanish Ministry of Economy and Competitiveness (grant n° IEDI-2016-00690). MSC received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310. H.H.H.A. was supported by ZonMW grant numbers 916.19.15 and 916.19.151. J.D.G. holds a 'Ramón y Cajal' fellowship (RYC-2013-13054).