Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis.
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.
Kato
S
S
Division of Neuropathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Hayashi
H
H
Nakashima
K
K
Nanba
E
E
Kato
M
M
Hirano
A
A
Nakano
I
I
Asayama
K
K
Ohama
E
E
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D001253:Astrocytes / Q000473:pathology* / Q000648:ultrastructure; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006818:Hyalin / Q000648:ultrastructure*; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure