HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

Review

Recent advances in research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations: Neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions

S. Kato, M. Saito, A. Hirano and E. Ohama

The Division of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan and the Division of Neuropathology, Department of Pathology, Montefiore Medical Center, Bronx, New York, USA

Offprint requests to: Dr. Shinsuke Kato, Division of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Nishi-machi 86, Yonago 683-8503, Japan. Fax: 81-859-34-8289

 

Summary. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Of all patients with ALS, approximately 5%-10% of them are familial and most of the others are sporadic. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. FALS is neuropathologically classified into two subtypes: classical FALS in which degeneration is restricted to only motor neurons and FALS which is characterized by the degeneration of the posterior column in addition to the lesion of the motor neuron system. The neuronal Lewy body-like hyaline inclusion (LBHI) is a characteristic neuropathological marker of mutant SOD1-linked FALS with posterior column involvement. Inclusions similar to the neuronal LBHIs have been discovered in astrocytes in certain patients with FALS exhibiting SOD1 gene mutations. The purpose of this review is to discuss the novel neuropathological significance of the astrocytic hyaline inclusions (Ast-HIs) and neuronal LBHIs in brain tissues from individuals with the posterior-column-involvement-type FALS with SOD1 gene mutations. In hematoxylin and eosin preparations, both Ast-HIs and neuronal LBHIs are eosinophilic inclusions and sometimes show eosino-philic cores with paler peripheral halos. Immunohisto-chemically, both inclusions are intensely positive for SOD1. At the ultrastructural level, both inclusions consist of approximately 15-25 nm-sized granule-coated fibrils and granular materials. Immunoelectron microscopically, these abnormal granule-coated fibrils and granular materials are positive for SOD1. Therefore, the FALS disease process originating from SOD1 gene mutations occurs in astrocytes as well as neurons and is involved in the formation of both inclusions. Histol. Histopathol. 14, 973-989 (1999)

 

Key words: Familial amyotrophic lateral sclerosis (FALS), Neuronal Lewy-body like hyaline inclusions (LBHIs), Astrocytic hyaline inclusions (Ast-HIs), Superoxide dismutase 1 (SOD1), Granule-coated fibrils

DOI: 10.14670/HH-14.973