FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

Neuropathol Appl Neurobiol. 2012 Jun;38(4):322-8. doi: 10.1111/j.1365-2990.2011.01217.x.

Abstract

Aims: Recent studies have shown that fused-in-sarcoma (FUS) protein is a component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of patients with intranuclear inclusion body disease (INIBD). However, the extent and frequency of FUS-immunoreactive structures in INIBD are uncertain.

Methods: We immunohistochemically examined the brain, spinal cord and peripheral ganglia from five patients with INIBD and five control subjects, using anti-FUS antibodies.

Results: In controls, the nuclei of both neurones and glial cells were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord were positive for FUS. FUS-positive INIBs were also found in the peripheral ganglia. The proportion of FUS-positive neuronal INIBs relative to the total number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%) and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%). The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no FUS immunoreactivity.

Conclusions: These findings suggest that FUS is incorporated into INIBs in both neurones and glial cells and that loss of normal FUS immunoreactivity may result from reduced protein expression and/or sequestration within inclusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Intranuclear Inclusion Bodies / immunology
  • Intranuclear Inclusion Bodies / metabolism*
  • Intranuclear Inclusion Bodies / pathology
  • Middle Aged
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neuroglia / immunology
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Neurons / immunology
  • Neurons / metabolism*
  • Neurons / pathology
  • RNA-Binding Protein FUS / immunology
  • RNA-Binding Protein FUS / metabolism*
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • RNA-Binding Protein FUS