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Influence of Apolipoprotein E  4 Genotype on Brain Tissue Integrity in Relapsing-Remitting Multiple Sclerosis
Nicola De Stefano, MD;
Maria Letizia Bartolozzi, MD;
Benedetta Nacmias, MD;
Valentina Zipoli, MD;
Marzia Mortilla, MD;
Leonello Guidi, MD;
Gianfranco Siracusa, MD;
Sandro Sorbi, MD;
Antonio Federico, MD;
Maria Pia Amato, MD
Arch Neurol. 2004;61:536-540.
Background Recent clinical and imaging studies have raised the hypothesis that patients with multiple sclerosis (MS) and the apolipoprotein E (ApoE)  4 allele may have a more severe disease course than those without the ApoE 4 allele. This seems to be related to more extensive tissue destruction and less efficient neuronal maintenance and repair in ApoE 4 carriers.
Objective To evaluate the influence of different ApoE genotypes on brain tissue integrity in patients with relapsing-remitting MS (RRMS).
Design We determined the ApoE genotype in 76 RRMS patients. Conventional T1-, T2-, and proton density–weighted magnetic resonance (MR) images were obtained for each patient and in a group of demographically matched healthy control subjects. On conventional T1-weighted MR images, an automated analysis tool was used to obtain total brain volumes normalized for head size (NBVs). Total brain lesion load was estimated on proton density– and T2-weighted MR images.
Results From the whole group of RRMS patients, we identified 18 with and 58 without the 4 allele. Both patient groups were not significantly different in age, age of disease onset, clinical disability, and disease duration. Carriers of the 4 allele showed significantly (P = .01) lower NBVs than controls and non–4 allele carriers. When a similar analysis was performed on only those patients with both very short disease duration and absence of clinical disability, NBV values were still significantly lower in RRMS patients with the 4 allele than in those without it (P = .02) and in controls (P = .007). In contrast, RRMS patients with different ApoE genotypes did not show significant differences in values of total brain T2-weighted lesion volumes.
Conclusions The presence of significant NBV decreases only in the group of RRMS patients with the ApoE 4 genotype provides new evidence that links ApoE 4–related impaired mechanisms of cell repair and severe tissue destruction in MS. Results of the present study suggest that this negative influence of the ApoE 4 genotype might be active from the earliest disease stages.
From the Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy (Drs De Stefano, Mortilla, and Federico); the Neurology Unit, Hospital of Empoli, Empoli, Italy (Drs Bartolozzi and Guidi), and the Department of Neurology, University of Florence, Florence, Italy (Drs Nacmias, Zipoli, Siracusa, Sorbi, and Amato).
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