Lower levels of N-acetylaspartate in multiple sclerosis patients with the apolipoprotein E epsilon4 allele.
BACKGROUND
In multiple sclerosis (MS), the epsilon4 allele of apolipoprotein E (APOE epsilon4) has been associated with more rapid clinical worsening and more severe tissue damage on magnetic resonance imaging.


OBJECTIVE
To use proton magnetic resonance spectroscopy ((1)H-MRS) to further explore the biochemical changes in the brains of patients with MS associated with APOE epsilon4.


METHODS
A 2-year clinical and (1)H-MRS follow-up cohort study.


METHODS
The MS outpatient clinic, Department of Neurology, and Magnetic Resonance Center of Karl-Franzens University.


METHODS
We performed (1)H-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.


METHODS
Levels of N-acetylaspartate as measured by (1)H-MRS.


RESULTS
Patients with MS and an epsilon4 allele (n = 19) had a significantly lower mean +/- SD N-acetylaspartate-creatine ratio than those without an epsilon4 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 epsilon4 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 (Delta)Expanded Disability Status Scale score, 0.9 +/- 1.8 vs 0.3 +/- 1.1; P =.19).


CONCLUSIONS
The APOE epsilon4 allele has a negative effect on the course of MS, and increasing axonal damage may be an important mechanism.
Enzinger
Christian
C
Department of Neurology, Karl-Franzens University, Graz, Austria.
Ropele
Stefan
S
Strasser-Fuchs
Siegrid
S
Kapeller
Peter
P
Schmidt
Helena
H
Poltrum
Birgit
B
Schmidt
Reinhold
R
Hartung
Hans-Peter
HP
Fazekas
Franz
F
D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000097:blood*; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D011522:Protons
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate