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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; Operto, Grégory; Evans, Tavia E; Falcon, Carles; Crous-Bou, Marta; Minguillón, Carolina; Cacciaglia, Raffaele; Milà-Alomà, Marta; Grau-Rivera, Oriol; Suárez-Calvet, Marc; Garrido-Martín, Diego; Morán, Sebastián; Esteller, Manel; Adams, Hieab H; Molinuevo, José Luis; Guigó, Roderic; Gispert, Juan Domingo.
Affiliation
  • Vilor-Tejedor N; Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, C. Doctor Aiguader 88, Edif. PRBB, 08003, Barcelona, Spain. natalia.vilortejedor@crg.eu.
  • Operto G; Barcelonaßeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain. natalia.vilortejedor@crg.eu.
  • Evans TE; Erasmus MC University Medical Center Rotterdam, Department of Clinical Genetics, Rotterdam, The Netherlands. natalia.vilortejedor@crg.eu.
  • Falcon C; Universitat Pompeu Fabra (UPF), Barcelona, Spain. natalia.vilortejedor@crg.eu.
  • Crous-Bou M; Barcelonaßeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
  • Minguillón C; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
  • Cacciaglia R; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
  • Milà-Alomà M; Erasmus MC University Medical Center Rotterdam, Department of Clinical Genetics, Rotterdam, The Netherlands.
  • Grau-Rivera O; Barcelonaßeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
  • Suárez-Calvet M; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
  • Garrido-Martín D; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
  • Morán S; Barcelonaßeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
  • Esteller M; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Adams HH; Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Hospitalet de Llobregat, Barcelona, Spain.
  • Molinuevo JL; Barcelonaßeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
  • Guigó R; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
  • Gispert JD; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Brain Struct Funct ; 225(8): 2331-2345, 2020 Nov.
Article in En | MEDLINE | ID: mdl-32804326
ABSTRACT

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.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apolipoproteins E / Cognition / Brain-Derived Neurotrophic Factor / Polymorphism, Single Nucleotide / Hippocampus Type of study: Prognostic_studies Limits: Female / Humans / Male / Middle aged Language: En Journal: Brain Struct Funct Journal subject: CEREBRO Year: 2020 Document type: Article Affiliation country: España

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apolipoproteins E / Cognition / Brain-Derived Neurotrophic Factor / Polymorphism, Single Nucleotide / Hippocampus Type of study: Prognostic_studies Limits: Female / Humans / Male / Middle aged Language: En Journal: Brain Struct Funct Journal subject: CEREBRO Year: 2020 Document type: Article Affiliation country: España
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