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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
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