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Neuropathology of familial amyotrophic lateral sclerosis patients with superoxide dismutase 1 gene mutation
Author(s) -
Hirano Asao
Publication year - 1998
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.1998.tb00132.x
Subject(s) - amyotrophic lateral sclerosis , sod1 , neuropathology , neurofilament , anterior horn cell , pathology , mutation , superoxide dismutase , atrophy , biology , lewy body , tardbp , microbiology and biotechnology , medicine , genetics , gene , parkinson's disease , biochemistry , immunohistochemistry , disease , oxidative stress
More than 60 mutations of the copper/zinc superoxide dismutase 1 (SOD1) gene have been identified. We are aware of 19 reported autopsied cases of familial amyotrophic lateral sclerosis (ALS) linked to these mutations. A review of these cases disclosed remarkable heter‐ogenicity of ALS, not only in molecular genetics but also clinicopathologically. However, it is noteworthy that all patients with alanine to valine substitution at codon 4 (A4V) mutation of SOD1 in familial ALS apparently disclose a distinct characteristic phenotype. All these patients manifested a rapid course of progressive muscular atrophy and died less than 1 year after the onset of illness. Microscopic findings were essentially identical in three cases: (i) marked loss of anterior horn neurons and Clarke's nuclei; (ii) the presence of intracytoplasmic Lewy body like hyalin inclusions and cord‐like enlargements of the processes in some of the affected neurons. The Lewy body like inclusions were also recognized by antibodies to phos‐phorylated neurofilaments protein, ubiquitin, and SOD1. Under electron microscopy, the inclusions consisted of a network of 10 nm neurofilaments intermingled with ill‐defined coarse linear structures; (iii) degeneration of spinocerebellar tracts, and middle root zone of the posterior column.