Quantitation of the Myelin‐Associated Glycoprotein in Human Nervous Tissue from Controls and Multiple Sclerosis Patients

Abstract

Myelin-associated glycoprotein (MAG) was measured by radioimmunoassay in the human CNS and peripheral nervous system (PNS). The level of MAG, expressed as ng/.mu.g of total protein, was .apprx. 20-fold higher in whole homogenates of cerebral white matter (4.7 .+-. 0.60) than of peripheral nerve (0.12-0.28). MAG concentrations were only slightly higher in the isolated myelin fractions from these tissues: CNS myelin, 5.6 ng/.mu.g; PNS myelin, 0.37 ng/.mu.g. The levels of MAG were measured in nine plaques, periplaque regions, and areas of macroscopically normal-appearing white matter (NAWM) from six separate multiple sclerosis brains and compared with the levels of other myelin proteins in the same samples. MAG and other myelin proteins was reduced to very low levels in plaques. The levels of MAG and basic protein (BP) and the activity of 2'',3''-cyclic nucleotide 3''-phosphodiesterase (CNP) in periplaque areas were significantly lower than those in control white matter, and MAG and BP levels were also significantly reduced in NAWM. In a periplaque region and NAWM from the most rapidly progressing case of multiple sclerosis examined, the MAG content was between 30 and 35% of the control level, whereas BP and PLP levels and CNP activity were between 50 and 85% of control values. The reduction of MAG content in periplaque regions from all nine multiple sclerosis plaques examined was significantly greater than the reductions of BP level and CNP activity. In NAWM samples, the mean reduction of MAG content was also greater than the reductions of BP level and CNP activity, but the difference was only statistically significant in comparison to CNP. These quantitative biochemical studies support earlier immunocytochemical observations suggesting that the MAG level is reduced more than levels of other myelin proteins at the periphery of some multiple sclerosis plaques.