EXPRESSION OF THE ADRENOLEUKODYSTROPHY PROTEIN IN THE HUMAN AND MOUSECENTRAL-NERVOUS-SYSTEM

The gene mutated in X-linked adrenoleukodystrophy (ALD), a progressive demyelinating disease, codes for a protein (ALDP) involved in very-lo ng-chain fatty acid (VLCFA) transport. The expression of ALDP and of t wo peroxisomal enzymes involved in beta-oxidation of VLCFA, acyl-CoA o xidase, and catalase was studied in human and mouse brain. The pattern of expression was similar in both species. While acyl-CoA oxidase and catalase are found in all types of CNS cells, including neurons and o ligodendrocytes, ALDP expression is restricted mostly to the white mat ter and endothelial cells. ALDP is highly expressed in astrocytes and microglial cells in vivo and in regenerating oligodendrocytes in vitro . In contrast, in vivo, ALDP is detected in much fewer oligodendrocyte s and quantitative Western blot analysis confirmed the lower abundance of ALDP in these cells than in astrocytes, Only oligodendrocytes loca lized in corpus callosum, internal capsules, and anterior commissure e xpress ALDP at levels comparable to those seen in astrocytes. In ALD, demyelination is first detected in these white matter regions, suggest ing that the ALD gene mutation selectively affects those oligodendrocy tes strongly expressing ALDP. Because of their failure to express ALDP , microglia and astrocytes may also contribute to demyelination in ALD patients. (C) 1997 Academic Press.