Neuropathology of familial amyotrophic lateral sclerosis patients with superoxide dismutase 1 gene mutation

Asao Hirano

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 heterogenicity 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 phosphorylated 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.

Original languageEnglish (US)
Pages (from-to)363-369
Number of pages7
JournalNeuropathology
Volume18
Issue number4
StatePublished - 1998

Fingerprint

Lewy Bodies
Mutation
Spinocerebellar Tracts
Anterior Horn Cells
Genes
Neurofilament Proteins
Spinal Muscular Atrophy
Hyalin
Intermediate Filaments
Amyotrophic Lateral Sclerosis
Valine
Ubiquitin
Codon
Alanine
Zinc
Copper
Molecular Biology
Electron Microscopy
Phenotype
Neurons

Keywords

  • Amyotrophic lateral sclerosis
  • Lewy body like hyalin inclusions
  • Superoxide dismutase 1 gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Neuropathology of familial amyotrophic lateral sclerosis patients with superoxide dismutase 1 gene mutation. / Hirano, Asao.

In: Neuropathology, Vol. 18, No. 4, 1998, p. 363-369.

Research output: Contribution to journalArticle

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