SAN DIEGO—Two studies presented at the 52nd Annual Meeting of the American Academy of Neurology explored apolipoprotein E (APOE) genotype and serum level as indicators of multiple sclerosis disease activity, differentiation of disease subtype, and response to therapy. Data presented by Joab Chapman, MD, and colleagues showed that the APOE*E4 allele is associated with significantly faster progression to disability; however, data from another study (presented by Ercan Elitok, MD, and colleagues) showed that although ApoE serum level may be a useful marker of clinical subtype, it is not a useful marker of disease progression or the response of the disease to therapy.

A "BAD PROGNOSTIC FACTOR"

"It seems that the APOE*E4 allele is a general bad prognostic factor for neurologic disease," said Dr. Chapman, a Senior Lecturer in the Department of Neurology at Tel Aviv University, Israel. "Many reports correlate its effects in Alzheimer's disease. It is also, perhaps, not so specific. It makes whatever is happening in Alzheimer's disease worse. The brain cannot repair itself properly, because APOE*E4 is somehow not doing the job as well as APOE*E3. So when you're young, it's okay; but when you get some kind of neurologic disease, then it comes into play," he explained.

Dr. Chapman and colleagues previously reported the association of the APOE*E4 allele and significantly faster disease progression seen in a two-year follow-up study. The present study extended their findings by examining a larger group of patients (205). They were diagnosed with clinically definite multiple sclerosis, and they were followed for up to 40 years. Forty-one of the patients were APOE*E4 carriers and 164 of the patients were noncarriers.

Disease progression was ranked according to the expanded disability status scale (EDSS) score. APOE*E4 carriers reached the EDSS score of 4.0 more quickly than did noncarriers—half of them reached 4.0 in seven years compared with 19. Similarly, more APOE*E4 carriers than noncarriers reached (and did so more quickly) an EDSS score of 6.0. Within 14 years, 50% of the APOE*E4 group had reached a score of 6.0, while within 25 years, a similar proportion of the noncarriers had reached a score of 6.0. APOE*E4 is the first genetic factor to be identified as having such a major impact on the disease.

Progression, noted the researchers, was slightly faster in males than in females. They also noted that the APOE*E4 allele was associated with a slightly earlier age of disease onset. However, the percentage of subjects with multiple sclerosis who were also carriers of the APOE*E4 allele (20%) was similar to that of the general Israeli population.

DISEASE SUBTYPE, NOT PROGRESSION

In a study of the association between ApoE serum level and multiple sclerosis progression, Dr. Elitok and colleagues followed 27 patients (15 female; age, 24 to 55) with relapsing-remitting multiple sclerosis for up to 14 months, and 15 patients (10 male; age, 35 to 60) with primary progressive multiple sclerosis for up to six months. Dr. Elitok is a Resident with the Department of Neurology at the University of Ulm, Germany.

Serial serum samples were drawn from the cohort. Serum enzyme levels were correlated with disease progression as indicated by EDSS scores, by new lesions on magnetic resonance imaging (MRI), and by relapses. Dr. Elitok and colleagues found no significant correlation between ApoE serum level, EDSS score, or new MRI lesion in relapsing-remitting multiple sclerosis. Nor did they find a correlation between ApoE serum level in primary progressive multiple sclerosis and response to interferon beta-1b therapy.

Although ApoE serum level did not indicate disease activity, it did indicate disease subtype. In patients with relapsing-remitting multiple sclerosis, the median ApoE serum level was 50.97 mg/L, while in those with primary progressive multiple sclerosis, the median ApoE serum level was 71.20 mg/L. Dr. Elitok and colleagues concluded that the correlation of serum level and disease subtype suggests "different pathogenic mechanisms."

NR