ADVANCED LIPID-PEROXIDATION END-PRODUCTS IN ALEXANDERS-DISEASE

Rosenthal fibers (RF), intra-astrocytic hyaline inclusions, accumulate in various pathological conditions and are the histological hallmark of Alexander's disease. While the major protein components of RF have been identified, the factors accounting for their pathogenesis, accumu lation, and insolubility are largely unknown. In this study, we immuno histochemically examined three cases of Alexander's disease using anti bodies to a lysine-derived pyrrole modification arising from 4-hydroxy -2-nonenal, a highly cytotoxic reactive aldehyde produced by lipid per oxidation. In all the cases of Alexander's disease examined, strong im munolabeling of RF by the antibodies to 4-hydroxy-2-nonenal pyrrole ad ducts were noted. By contrast, age-matched control cases showed no imm unoreactivity. These results indicate that modification of protein by lipid peroxidation adducts may play an important role in the formation of RF as well as in the pathogenesis of Alexander's disease. Furtherm ore, taken together with our previous data indicating advanced Maillar d reaction end products in RF, it seems that post-translational modifi cation of RF, initiated by oxidative stress, is critical for both the accumulation and the insolubility of RF, and therefore, by inference, in the pathogenesis of Alexander's disease. (C) 1998 Elsevier Science B.V.