Abstract
BackgroundCurrent 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.MethodsBDNF 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.ResultsBDNF 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.ConclusionTo 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.
Highlights
Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders (Bathina and Das 2015; Autry and Monteggia 2012; Numakawa et al 2018)
Most of the studies addressing the association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and hippocampal volumes included patients of a variety of neuropsychiatric disorders, such as major depressive disorder, schizophrenia and bipolar disorder (Zeni et al 2016; Cao et al 2016; Reinhart et al 2015; Aas et al 2014; Frodl et al 2014), showing inconsistencies concerning the impact of the BDNF Val66Met polymorphisms (Tsai 2018)
We investigated whether the association between BDNF Val66Met and hippocampal subfield volumes was modified by the number of apolipoprotein E (APOE)-ε4 alleles, with a second model that included an interaction term between BDNF Val66Met polymorphism and the number of ε4 alleles, covarying for age, sex, years of education and total intracranial volume potential confounders
Summary
Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders (Bathina and Das 2015; Autry and Monteggia 2012; Numakawa et al 2018). Recent meta-analyses addressing hippocampal volumes for BDNF Val66Met have reported inconsistent statistically significant associations, as well as inconsistencies regarding the direction of the genotype effects across individual studies (Harrisberger et al 2014, 2015). To our knowledge no previous studies have addressed the effects of the BDNF Val66Met polymorphism on hippocampal subfields in cognitively unimpaired (CU) individuals. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders 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. 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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