Involvement of apolipoprotein E in multiple sclerosis: Absence of remyelination associated with possession of the APOE epsilon 2 allele

Lipids are a major constituent of myelin and apolipoprotein E (apoE) plays a key role in lipid transport. We therefore hypothesized that apoE is invol ved in the processes of demyelination and remyelination. Furthermore as the re is a biologically significant polymorphism in the APOE gene, the APOE ge notype may influence the course of multiple sclerosis (MS). Specifically, a s there is reduced affinity of the apoE E2 isoform for receptors on glial c ells, we hypothesized that remyelination is impaired in individuals with th e apoE epsilon 2 allele. We determined the apoE genotypes of 71 archival ca ses of multiple sclerosis and 41 controls, reviewed the neurohistology, and performed apoE immunohistochemistry. ApoE immunoreactivity was increased i n demyelinated areas compared with control white matter. ApoE immunostainin g was markedly increased in areas of active demyelination, specifically in macrophages and astrocytes. The APOE allele frequencies of the cases of MS (epsilon 2 = 0.06, epsilon 3 = 0.8, epsilon 4 = 0.13) resembled those of co ntrols. Evidence of remyelination was identified in 25/71 MS cases (35%): i n 25/64 patients (39%) without an epsilon 2 allele and 0/7 (0%) patients wi th an epsilon 2 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 pat ients with the APOE epsilon 2 allele.