White matter differences between healthy young ApoE4 carriers and non-carriers identified with tractography and support vector machines.

Laurence O'Dwyer,Silke Matura,Monika Scheibe,David Prvulovic,Julia Miller,Dan Rujescu,Franck Lamberton,Harald Hampel,Francisco José Esteban

doi:10.1371/journal.pone.0036024

Abstract

The apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20–38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4−). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age.

Highlights

Apolipoprotein E (ApoE) regulates the metabolism of lipids by coordinating their transport and redistribution from one cell type to another via ApoE receptors and proteins associated with lipid transfer and lipolysis [1]
The frequency of the apolipoprotein E4 (ApoE4) allele is low in humans, primate studies suggest that it is the ancestral allele and it has been hypothesized that the mutation leading to ApoE3 may have been selected for during the evolution of the unique role of grandmothering in early humans which led to the spread of the E3 allele [3]
The current results show that it is possible to classify healthy young ApoE4 carriers and non-carriers using an automated

Summary

Introduction

Apolipoprotein E (ApoE) regulates the metabolism of lipids by coordinating their transport and redistribution from one cell type to another via ApoE receptors and proteins associated with lipid transfer and lipolysis [1]. ApoE is thought to play a key role in neuronal development and brain plasticity [2]. Brain structure and function have been found to be altered in ApoE4 carriers, both in AD patients [6,7,8,9] 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 [6,15,16,17] and reduced medial temporal lobe volumes in healthy ApoE4 carriers across the age spectrum [14,18,19,20,21]. A mixed picture is found in terms of functional studies, with both increased [6,9,25] and decreased [26,27] task-related BOLD signals reported in carrier groups relative to non-carriers

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