LECITHIN-CHOLESTEROL ACYLTRANSFERASE IN HUMAN CEREBROSPINAL-FLUID - REDUCED LEVEL IN PATIENTS WITH MULTIPLE-SCLEROSIS AND EVIDENCE OF DIRECT SYNTHESIS IN THE BRAIN

Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated impairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06-mu-g/ml (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4-mu-g/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06 +/- 0.02-mu-g/ml). Lipoprotein (a) concentration was below the sensitivity of the enzyme immunoassay used for the measurement (< 40 ng/ml) in cerebrospinal fluid from both control subjects and those with demyelinating disease or multiple sclerosis.