FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS mutation

Naoki Suzuki, Shinsuke Kato, Masako Kato, Hitoshi Warita, Hideki Mizuno, Masaaki Kato, Naoko Shimakura, Haruhiko Akiyama, Zen Kobayashi, Hidehiko Konno, Masashi Aoki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Basophilic inclusions (BIs) are pathological features of a subset offrontotemporal lobar degeneration disorders, including sporadic amyotrophic lateral sclerosis (ALS) and familial ALS (FALS). Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have recently been identified as a cause of FALS. The FUS/TLS-immunoreactive inclusions are consistently found in cases of frontotemporal lobar degeneration with BIs; however, the association between ALS cases with BIs and FUS/TLS accumulation is not well understood. We used immunohistochemistry to analyze 3 autopsy cases of FALS with the FUS/TLS mutation and with BIs using anti-FUS/TLS antibodies. The disease durations were 1, 3, and 9 years. As the disease duration becomes longer, there were broader distributions of neuronal and glial FUS/TLS-immunoreactive inclusions. As early as 1 year after the onset, BIs, neuronal cytoplasmic inclusions and glial cytoplasmic inclusions were found in the substantia nigra in addition to the anterior horn of the spinal cord. Glial cytoplasmic inclusions are found earlier and in a wider distribution than neuronal cytoplasmic inclusions. The distribution of FUS/TLS-immunoreactive inclusions in FUS/TLS-mutated FALS with BIs was broader than that of BIs alone, suggesting that the pathogenetic mechanism may have originated from the FUS/TLS proteinopathy.

Original languageEnglish
Pages (from-to)779-788
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume71
Issue number9
DOIs
Publication statusPublished - 2012 Sep 1

Keywords

  • Autopsy
  • Basophilic inclusions
  • Familial amyotrophic lateral sclerosis
  • Fused in sarcoma/translocated in liposarcoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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