Effect of BDNFVal66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study

Background Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the epsilon 4 allele ofAPOEgene 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 BDNFVal66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-epsilon 4 status. Methods BDNFVal66Met andAPOEgenotypes 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 BDNFVal66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-epsilon 4 alleles and total intracranial volume. We also investigated whether the association between APOE-epsilon 4 allele and HSv were modified by BDNFVal66Met genotypes. Results BDNFVal66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated withAPOE-epsilon 4 allele were significantly moderated by BDNFVal66Met status.BDNFMet carriers who were alsoAPOE-epsilon 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 theBDNFVal66Met polymorphisms partially compensates the decreased on HSv associated withAPOE-epsilon 4 in middle-age cognitively unimpaired individuals.