Imaging genetics in multiple sclerosis: A volumetric and diffusion tensor MRI study of APOE ε4

Evidence linking the epsilon 4 allele of APOE to more severe brain MRI abnormalities in multiple sclerosis (MS) has been conflicting and limited to studies of lesion load and whole brain atrophy. The purpose of the present study was to determine whether the epsilon 4 allele of APOE is associated with more extensive brain pathology in MS using structural and diffusion tensor MRI. Using a case-control design, 43 MS patients with the 64 allele and 47 epsilon 4 negative MS patients underwent structural and diffusion tensor imaging (DTI) at 3T. Hypo- and hyperintense lesion volumes, whole brain and medial temporal volumes, and DTI parameters (fractional anisotropy (FA) and mean diffusivity (MD)) in normal-appearing brain tissue and lesions were compared between the groups. epsilon 4+ and epsilon 4- MS patients were well-matched on demographic characteristics, disease variables, and proportions receiving disease-modifying therapy. epsilon 4+ and epsilon 4- patients did not differ on any MRI or DTI measure. This study refutes a role for the epsilon 4 allele in MRI abnormalities in MS, particularly those linking epsilon 4 to greater T1 hypointense lesion volume and brain atrophy. Previous work on this putative gene-MRI relationship is extended by comparing DTI measures within lesions and normal-appearing brain tissue. A lack of differences in medial temporal regions, areas that have been linked to epsilon 4-associated changes in health and disease, further supports the conclusion that that epsilon 4 is not associated with more subtle MRI markers of brain pathology in MS. (C) 2011 Elsevier Inc. All rights reserved.