Involvement of Apolipoprotein E in Multiple Sclerosis: Absence of Remyelination Associated with Possession of theAPOEε2 Allele
Autor: | Lilian S. Murray, Christopher Carlin, David I. Graham, D. Doyle, James A. R. Nicoll |
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Rok vydání: | 2000 |
Předmět: |
Adult
Male Apolipoprotein E Multiple Sclerosis Genotype Apolipoprotein E2 Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience Myelin Apolipoproteins E Gene Frequency Reference Values medicine Humans Remyelination Allele Allele frequency Alleles Myelin Sheath Aged Aged 80 and over Multiple sclerosis Brain General Medicine Middle Aged medicine.disease Immunohistochemistry medicine.anatomical_structure Neurology Immunology Female lipids (amino acids peptides and proteins) Neurology (clinical) |
Zdroj: | Journal of Neuropathology & Experimental Neurology. 59:361-367 |
ISSN: | 1554-6578 0022-3069 |
Popis: | Lipids are a major constituent of myelin and apolipoprotein E (apoE) plays a key role in lipid transport. We therefore hypothesized that apoE is involved in the processes of demyelination and remyelination. Furthermore as there is a biologically significant polymorphism in the APOE gene, the APOE genotype may influence the course of multiple sclerosis (MS). Specifically, as there is reduced affinity of the apoE E2 isoform for receptors on glial cells, we hypothesized that remyelination is impaired in individuals with the apoE epsilon2 allele. We determined the apoE genotypes of 71 archival cases of multiple sclerosis and 41 controls, reviewed the neurohistology, and performed apoE immunohistochemistry. ApoE immunoreactivity was increased in demyelinated areas compared with control white matter. ApoE immunostaining was markedly increased in areas of active demyelination, specifically in macrophages and astrocytes. The APOE allele frequencies of the cases of MS (epsilon2 = 0.06, epsilon3 = 0.8, epsilon4 = 0.13) resembled those of controls. Evidence of remyelination was identified in 25/ 71 MS cases (35%): in 25/64 patients (39%) without an epsilon2 allele and 0/7 (0%) patients with an epsilon2 allele (p < 0.05). In conclusion, we provide evidence that apoE is involved in the trafficking of lipid in MS and, although the number of cases with this allele was small, remyelination may be defective in patients with the APOE epsilon2 allele. |
Databáze: | OpenAIRE |
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