An autopsied case of sporadic adult-onset amyotrophic lateral sclerosis with FUS-positive basophilic inclusions

Authors

  • Takeshi Matsuoka,

    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author
  • Naoki Fujii,

    1. Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Tachibana, Omuta, and
    Search for more papers by this author
  • Akira Kondo,

    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author
  • Akiko Iwaki,

    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    Search for more papers by this author
  • Toshihiro Hokonohara,

    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    Search for more papers by this author
  • Hiroyuki Honda,

    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author
  • Kensuke Sasaki,

    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author
  • Satoshi O. Suzuki,

    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author
  • Toru Iwaki

    Corresponding author
    1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashiku,
    Search for more papers by this author

  • Declaration of Conflict of interest: The authors have no conflicts of interest.

Toru Iwaki, MD, PhD, Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Email: iwaki@np.med.kyushu-u.ac.jp

Abstract

Basophilic inclusions (BIs), which are characterized by their staining properties of being weakly argyrophilic, reactive with Nissl staining, and immunohistochemically negative for tau and transactive response (TAR) DNA-binding protein 43 (TDP-43), have been identified in patients with juvenile-onset amyotrophic lateral sclerosis (ALS) and adult-onset atypical ALS with ophthalmoplegia, autonomic dysfunction, cerebellar ataxia, or a frontal lobe syndrome. Mutations in the fused in sarcoma gene (FUS) have been reported in cases of familial and sporadic ALS, and FUS immunoreactivity has been demonstrated in basophilic inclusion body disease (BIBD), neuronal intermediate filament inclusion disease (NIFID), and atypical frontotemporal lobar degeneration with ubiquitin-positive and tau-negative inclusions (aFTLD-U). In the present study, we immunohistochemically and ultrastructurally studied an autopsy case of sporadic adult-onset ALS with numerous BIs. The patient presented with the classical clinical course of ALS since 75 years of age and died at age 79. Postmortem examination revealed that both Betz cells in the motor cortex and motor neurons in the spinal cord were affected. The substantia nigra was spared. Notably, BIs were frequently observed in the motor neurons of the anterior horns, the inferior olivary nuclei, and the basal nuclei of Meynert. BIs were immunopositive for p62, LC3, and FUS, but immunonegative for tau, TDP-43, and neurofilament. Ultrastructurally, BIs consisted of filamentous or granular structures associated with degenerated organelles with no limiting membrane. There were no Bunina bodies, skein-like inclusions, or Lewy-like inclusions. All exons and exon/intron boundaries of the FUS gene were sequenced but no mutations were identified.

Ancillary