Abstract
Many studies have shown that healthy elderly subjects and patients with Alzheimer’s disease (AD) who carry the apolipoprotein E (ApoE) ε4 allele have worse cognitive function and more severe brain atrophy than non-carriers. However, it remains unclear whether this ApoE polymorphism leads to changes of cognition and brain morphology in healthy young adults. In this study, we used an established model to measure verbal episodic memory and core executive function (EF) components (response inhibition, working memory and task switching) in 32 ApoE ε4 carriers and 40 non-carriers between 20 years and 40 years of age. To do this, we carried out an adapted auditory verbal learning test and three computerized EF tasks. High-resolution head magnetic resonance scans were performed in all participants and voxel-based morphometry (VBM) was used for image processing and analysis. Multivariate analysis of variance (ANOVA) performed on memory measures showed that the overall verbal episodic memory of ApoE ε4 carriers was significantly worse than non-carriers (Wilk’s λ = 4.884, P = 0.004). No significant differences were detected in overall EF between the two groups. Post hoc analyses revealed group differences in terms of immediate recall, recognition and task switching, which favored non-carriers. VBM analysis showed gray matter (GM) bilateral reductions in the medial and dorsolateral frontal, parietal and left temporal cortices in the carrier group relative to the non-carrier group, which were most significant in the bilateral anterior and middle cingulate gyri. However, these changes in GM volume were not directly associated with changes in cognitive function. Our data show that the ApoE ε4 allele is associated with poorer performance in verbal episodic memory and task switching, and a reduction in GM volume in healthy young adults, suggesting that the effects of ApoE ε4 upon cognition and brain morphology exist long before the possible occurrence of AD.
Highlights
The ε4 allele of apolipoprotein E (ApoE) is the most clearly defined genetic risk factor for sporadic Alzheimer’s disease (AD)
The effects of ApoE gene polymorphisms upon brain morphology and cognitive function are not limited to AD patients; brain atrophy and cognition impairment associated with ApoE ε4 carriers were found in studies of healthy elderly subjects (Honea et al, 2009; Crivello et al, 2010; Lu et al, 2011) and in non-AD patients with neurological disorders, such as frontotemporal dementia (Boccardi et al, 2004; Agosta et al, 2009), Parkinson’s disease (Mata et al, 2014) and HIV infection (Wendelken et al, 2016)
We hypothesized that the effects of ApoE polymorphism on brain morphology and function may have no specific relationship with the pathophysiological process of AD, but is more likely to affect brain growth and development, aging and pathological repair through specific mechanisms, which increases the risk of neurological diseases in ApoE ε4 carriers
Summary
The ε4 allele of apolipoprotein E (ApoE) is the most clearly defined genetic risk factor for sporadic Alzheimer’s disease (AD). Carriers of the ε4 allele are at an increased risk of AD and have a significantly earlier onset age of AD (Shaw et al, 2007; Chang et al, 2016) It is still not clear how ApoE gene polymorphism is involved in the pathogenesis of AD. The effects of ApoE gene polymorphisms upon brain morphology and cognitive function are not limited to AD patients; brain atrophy and cognition impairment associated with ApoE ε4 carriers were found in studies of healthy elderly subjects (Honea et al, 2009; Crivello et al, 2010; Lu et al, 2011) and in non-AD patients with neurological disorders, such as frontotemporal dementia (Boccardi et al, 2004; Agosta et al, 2009), Parkinson’s disease (Mata et al, 2014) and HIV infection (Wendelken et al, 2016). We hypothesized that the effects of ApoE polymorphism on brain morphology and function may have no specific relationship with the pathophysiological process of AD, but is more likely to affect brain growth and development, aging and pathological repair through specific mechanisms, which increases the risk of neurological diseases in ApoE ε4 carriers
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