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American Journal of Pathology, Vol 151, 611-620, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis

S Kato, H Hayashi, K Nakashima, E Nanba, M Kato, A Hirano, I Nakano, K Asayama and E Ohama
Division of Neuropathology, Faculty of Medicine, Tottori University, Yonago, Japan.

To clarify the pathological characteristics of astrocytic hyaline inclusions (Ast-HIs) in patients with familial amyotrophic lateral sclerosis (FALS) with neuronal Lewy-body-like hyaline inclusions (LBHIs), eight autopsies on members of four different families, including two long-term surviving patients with clinical courses of over 10 years, were analyzed. Ast-HIs were found only in the two long- term surviving patients who belonged to different families and to different races. Ast-HIs were ultrastructurally composed of 15- to 25- nm granule-coated fibrils that had immunoreactivities to superoxide dismutase 1 (SOD1) and ubiquitin. Approximately 50% of the Ast-HIs expressed alpha B-crystallin, metallothionein, glutamine synthetase, and tubulin (alpha and beta) at various intensities. Some Ast-HIs reacted with antibodies to tau protein, S-100 protein, and heat shock protein 27. The Ast-HIs were not stained for glial fibrillary acidic protein. Our results suggest a cooperative role of superoxide dismutase 1, ubiquitin, and cytoskeletal proteins in the formation of granule- coated fibrils (namely, Ast-HIs) and provide evidence that Ast-HIs are formed in certain long-surviving familial amyotrophic lateral sclerosis patients with neuronal Lewy-body-like hyaline inclusions.

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