Abstract
The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20–38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4−), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.
Highlights
Apolipoprotein E (ApoE) plays a key role in neuronal development with signalling through ApoE receptors and proteins mediating processes including synaptic plasticity, neuronal survival and neurite outgrowth [1,2]
The volumes of each deep grey matter structure segmented by FMRIB’s Integrated Registration and Segmentation Tool (FIRST) were quantified in terms of both gross volume in mm3 (Table 2) and the volume normalised with total intracranial volume (Table 3)
The current results indicate that hippocampal volume is reduced in healthy young E4 carriers relative to non-carriers with the right hippocampus being more susceptible to atrophy than the left hippocampus
Summary
Apolipoprotein E (ApoE) plays a key role in neuronal development with signalling through ApoE receptors and proteins mediating processes including synaptic plasticity, neuronal survival and neurite outgrowth [1,2]. Brain structure and function have been found to be altered in ApoE4 carriers, both in AD patients [8,9] and in healthy subjects [10,11,12,13,14]. Studies have found greater rates of temporal lobe atrophy in AD patients with greater load of E4 allele [8,9,15,16] as well as reduced medial temporal lobe volumes in healthy ApoE4 carriers across the age spectrum [14,17,18,19,20]. Functional studies have reported both increased [7,17,24] and decreased [25,26] task-related BOLD signals in carrier groups relative to non-carriers
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