In multiple sclerosis (MS), the ϵ4 allele of apolipoprotein E (APOE ϵ4) has been associated with more rapid clinical worsening and more severe tissue damage on magnetic resonance imaging.
To use proton magnetic resonance spectroscopy (1H-MRS) to further explore the biochemical changes in the brains of patients with MS associated with APOE ϵ4.
A 2-year clinical and 1H-MRS follow-up cohort study.
The MS outpatient clinic, Department of Neurology, and Magnetic Resonance Center of Karl-Franzens University.
We performed 1H-MRS of the central portion of both hemispheres and APOE genotyping in 72 patients (52 women and 20 men; mean ± SD age, 34.8 ± 8.8 years) with clinically definite relapsing-remitting MS. Repeated studies were performed in 44 patients after a mean ± SD interval of 34 ± 9 months.
Main Outcome Measure
Levels of N-acetylaspartate as measured by 1H-MRS.
Patients with MS and an ϵ4 allele (n = 19) had a significantly lower mean ± SD N-acetylaspartate–creatine ratio than those without an ϵ4 allele (n = 53) (1.73 ± 0.26 vs 1.89 ± 0.24; P = .04) despite the absence of significant differences in age at onset, disease duration, Expanded Disability Status Scale score, and number of previous relapses between subgroups. During follow-up, the drop in the N-acetylaspartate–creatine ratio of ϵ4 carriers was also significantly larger (−0.31 vs −0.10; P = .01). This was paralleled by a higher number of relapses (mean ± SD, 4.1 ± 2.7 vs 1.7 ± 1.6; P = .02) and a faster although nonsignificant progression of disability (mean ± SD ΔExpanded Disability Status Scale score, 0.9 ± 1.8 vs 0.3 ± 1.1; P = .19).
The APOE ϵ4 allele has a negative effect on the course of MS, and increasing axonal damage may be an important mechanism.