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Imaging genetics in multiple sclerosis: a volumetric and diffusion tensor MRI study of APOE ε4
Omar Ghaffar1, Nancy J Lobaugh, Gregory M Szilagyi
1Brain Sciences Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. omar.ghaffar@utoronto.ca
Abstract:
Evidence linking the ε4 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 ε4 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 ε4 allele and 47 ε4 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. ε4+ and ε4- MS patients were well-matched on demographic characteristics, disease variables, and proportions receiving disease-modifying therapy. ε4+ and ε4- patients did not differ on any MRI or DTI measure. This study refutes a role for the ε4 allele in MRI abnormalities in MS, particularly those linking ε4 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 ε4-associated changes in health and disease, further supports the conclusion that that ε4 is not associated with more subtle MRI markers of brain pathology in MS.
Insights
The APOE ε4 allele does not worsen MRI abnormalities in multiple sclerosis (MS). This study found no link between the APOE ε4 allele and increased brain lesions or atrophy in MS patients.
Area of Science:
- Neuroimaging
- Genetics
- Neurology
Background:
- Conflicting evidence exists regarding the APOE ε4 allele's association with multiple sclerosis (MS) brain MRI abnormalities.
- Previous studies focused mainly on lesion load and whole brain atrophy, limiting comprehensive assessment.
Purpose of the Study:
- To investigate the association between the APOE ε4 allele and extensive brain pathology in MS using advanced MRI techniques.
- To determine if APOE ε4 influences structural and diffusion tensor imaging (DTI) measures in MS patients.
Main Methods:
- A case-control study compared 43 APOE ε4-positive (ε4+) and 47 ε4-negative (ε4-) MS patients.
- Structural and diffusion tensor imaging (DTI) were performed at 3T to assess lesion volumes, brain atrophy, and DTI parameters (FA, MD).
- Comparisons were made in normal-appearing brain tissue and lesions between the ε4+ and ε4- groups.
Main Results:
- No significant differences were observed in lesion volumes (T1 hypointense and hyperintense), whole brain volume, or medial temporal volumes between ε4+ and ε4- MS patients.
- Diffusion tensor imaging (DTI) parameters, including fractional anisotropy (FA) and mean diffusivity (MD), showed no differences in normal-appearing brain tissue or lesions between the groups.
- The groups were well-matched for demographics, disease variables, and disease-modifying therapy use.
Conclusions:
- This study refutes a role for the APOE ε4 allele in exacerbating MRI abnormalities in multiple sclerosis (MS).
- The findings indicate that APOE ε4 is not associated with increased lesion volume, brain atrophy, or subtle DTI changes in MS.
- Lack of differences in medial temporal regions further supports that APOE ε4 does not correlate with specific MRI markers of brain pathology in MS.
