論文

国際誌
2016年10月

Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis.

Neuropathology and applied neurobiology
  • T Onozato
  • ,
  • A Nakahara
  • ,
  • E Suzuki-Kouyama
  • ,
  • A Hineno
  • ,
  • T Yasude
  • ,
  • T Nakamura
  • ,
  • H Yahikozawa
  • ,
  • M Watanabe
  • ,
  • K Kayanuma
  • ,
  • H Makishita
  • ,
  • S Ohara
  • ,
  • T Hashimoto
  • ,
  • K Higuchi
  • ,
  • T Sakai
  • ,
  • K Asano
  • ,
  • T Hashimoto
  • ,
  • H Kanno
  • ,
  • J Nakayama
  • ,
  • K Oyanagi

42
6
開始ページ
561
終了ページ
72
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/nan.12310

AIMS: Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. METHODS: Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin-embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. RESULTS: (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p-neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p-independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43-immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. CONCLUSIONS: There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones.

リンク情報
DOI
https://doi.org/10.1111/nan.12310
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26819002
ID情報
  • DOI : 10.1111/nan.12310
  • PubMed ID : 26819002

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