Additional key phrases: apo E genotype; central nervous systemApolipoprotein E (apo E) is a polymorphic plasma protein involved in cholesterol transport. Apo E is produced and secreted in the central nervous system by astrocytes. Following peripheral nerve injury in rats, the synthesis of apo E increases 250-to 350-fold. A similar increase is observed in the central nervous system when the optic nerve and spinal cord are injured. It was suggested that apo E redistributes lipid, participates in cholesterol homeostasis in the brain and is implicated in the growth and repair of the nervous system. I Three common variants of apo E are present in the general human population, c2, d and fA coding for three isoforms (apo E2, apo E3, apo E4). These isoforms differ from each other by a single aminoacid substitution. The most frequent phenotype in the normal population is apo E3/ apo E3 and the two minor isoforms are associated with altered recognition of specific receptors. Recent genetic evidence suggests that inheritance of the c4 allele is associated with increased risk for sporadic and earlier onset of Alzheimer's disease (AD).2 In contrast, Rubinsztein found no influence of the apo E phenotype in a small group of patients with multiple sclerosis (MS).' MS is the major demyelinating disease. The increased higher incidence in women, the racial and familial clustering of MS cases and the high concordance rate in monozygotic twins (26%) compared with dizygotic twins (2'3%) and non twin siblings (1'9%), suggest that a genetic component influences susceptibility to MS. 4 We recently demonstrated that apo E concentrations in cerebrospinal fluid (CSF) and apo E intrathecal synthesis are decreased in MS patients. The reduction of CSF apo E levels may impair myelin repair and influence disease progression in MS patients.