Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis

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Abstract
OBJECTIVES Clinical reports have speculated on a more severe course of multiple sclerosis in patients with the apolipoprotein E (apoE) ε4 allele. As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype. METHODS Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of genotype patterns in multiple sclerosis. The total lesion load on proton density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional spin echo sequences at 1.5 T was measured. A “black hole” ratio ((T1-LL/T2-LL)×100) was also calculated. This indicates the proportion of multiple sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair. RESULTS Patients with the apoE-ε3/ε4 genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm3) than patients with the ε2/ε3 (n=11; 13.3 (9.5) cm3) or the ε3/ε3 genotype (n=49; 9.4 (SD 9.2) cm3). Both the T1-LL (2.6 (SD 3.3)v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm3; p=0.04) and the black hole ratio (14.3 SD 11.9)v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in ε3/ε4 patients. Similar differences were seen when comparing patients with at least one ε4 allele with the remainder of the group. CONCLUSIONS These data support speculations on a modulation of multiple sclerosis severity by the apoE genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the ε4 allele.