Influence of brain-derived neurotrophic-factor and apolipoprotein E genetic variants on hippocampal volume and memory performance in healthy young adults

Abstract

Unravelling the impact of genetic variants on clinical phenotypes is a challenging task. Apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) play an important role in cell growth, regeneration, synaptic plasticity, learning and memory processes. The aim of the present study was to examine the impact of BDNF Val66Met- and ApoE-polymorphisms and their interactions on hippocampal morphology and memory functions in healthy young adults. Hippocampal volume and memory performance of 135 healthy individuals, aged 24.6 ± 3.2 years, were assessed, using magnetic resonance imaging and the Inventory for Memory diagnostics. The performance of BDNF-Met66 carriers was significantly lower in working memory (P = 0.03) compared with non carriers, whereas no further differences were observed either in cognitive performance or in hippocampal volumes between the groups. Age, BDNF Val66 Met polymorphism and the interaction factor BDNF genotype x age were significantly associated with the variation of working memory scores (P = 0.01, 0.01, 0.02 respectively). No statistically significant differences were detected in the volumes of hippocampi and in memory phenotypes between individuals carrying the ApoE E4 allele and those without it. The analysis did not reveal an impact of gene-gene interaction between BDNF and ApoE genes on hippocampal volumes or memory performance. BDNF Val66Met polymorphism seems to influence working memory function and modulate the effects of ageing on working memory in healthy young adults.

The NTSR1 gene modulates the association between hippocampal structure and working memory performance

“…While this homogeneity is usually considered an advantage for genetic studies, avoiding the possible problem of ethnic stratification, it also limits the generalizability of our results to other populations. Previous studies have demonstrated that gene-brain-behavior relationships can be modulated by gender (Nemoto et al, 2006), ethnicity and/or culture (Mizuno et al, 2006;Munafo et al, 2008), and age (Nemoto et al, 2006;Richter-Schmidinger et al, 2010). Further studies are needed to replicate our results in other populations.…”

Hippocampal Volume Differences Between Healthy Young Apolipoprotein E ε2 and ε4 Carriers

“…The study protocol was approved by the local Ethics Committee and was previously described [5]. In brief, healthy young adults without history of somatic diseases potentially affecting brain function, current or past psychiatric disorders, medication (except hormonal contraceptives), pregnancy and magnetic resonance imaging (MRI) contraindications were enrolled in the study after giving their written informed consent.…”

“…Nevertheless, it has been speculated that the findings of studies based on elderly non-demented populations were biased by the sampling of individuals with incipient AD and by the relatively limited numbers of APOE 2 carriers due to the low prevalence of the 2 allele in the general population [4]. We have recently reported that differences were elucidated neither in hippocampal volumes nor in memory function between 18 healthy young adults possessing the APOE 4 allele and 117 APOE 4 non-carriers [5]. Upon further analysis of our research data we specifically extended our focus on the impact of the APOE 2 and 4 alleles on hippocampal morphology and memory function since the pathological hallmarks of AD emerge in the hippocampus, which is crucially involved in memory function [6].…”

APOE ε4 and cognitive function in early life: A meta-analysis.

“…Here, evidence has emerged that healthy young adults and children carrying the ɛ4 allele may in fact exhibit better cognitive performance relative to non-ɛ4 carriers (e.g., Acevedo, Piper, Craytor, Benice, & Raber, 2010;Alexander et al, 2007;Bloss, Delis, Salmon, & Bondi, 2010;Marchant, King, Tabet, & Rusted, 2010;Mondadori et al, 2007;Puttonen, Elovainio, Kivimaki, Lehtimaki, & Keltikangas-Jarvinen, 2003;Schultz et al, 2008;Wright et al, 2003;Yu, Lin, Chen, Hong, & Tsai, 2000). Equally though, there are studies which did not find differences in cognitive performance between young ɛ4 and non-ɛ4 carriers (e.g., Deary et al, 2003;Jorm et al, 2007;Luciano et al, 2009;Richter-Schmidinger et al, 2011;Ruiz et al, 2010;Taylor et al, in press;Turic, Fisher, Plomin, & Owen, 2001). In fact, there is also evidence that children and adolescents carrying the ɛ4 allele show poorer cognitive performance (e.g., Bloss, Delis, Salmon, & Bondi, 2008).…”