Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study.
APOE-ε4
BDNF
Hippocampal subfields
Imaging genetics
Subiculum
Val66Met
Journal
Brain structure & function
ISSN: 1863-2661
Titre abrégé: Brain Struct Funct
Pays: Germany
ID NLM: 101282001
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
23
04
2019
accepted:
30
07
2020
pubmed:
18
8
2020
medline:
12
8
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32804326
doi: 10.1007/s00429-020-02125-3
pii: 10.1007/s00429-020-02125-3
pmc: PMC7544723
doi:
Substances chimiques
Apolipoproteins E
0
Brain-Derived Neurotrophic Factor
0
Banques de données
ClinicalTrials.gov
['NCT01835717']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2331-2345Subventions
Organisme : European Union's Horizon 2020 Marie Sklodowska-Curie action
ID : 752310
Organisme : Health Department of the Catalan Government; Health Research and Innovation Strategic Plan (PERIS)
ID : SLT002/16/00201
Organisme : la Caixa Foundation
ID : LCF/PR/GN17/10300004
Organisme : Ministerio de Economía y Competitividad
ID : IEDI-2016-00690
Organisme : Ministerio de Economía y Competitividad
ID : RYC-2013-13054
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