ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

Hirotaka Tanaka, Masamitsu Shimazawa, Masafumi Takata, Hideo Kaneko, Kazuhiro Tsuruma, Tsunehiko Ikeda, Hitoshi Warita, Masashi Aoki, Mitsunori Yamada, Hitoshi Takahashi, Isao Hozumi, Hiroshi Minatsu, Takashi Inuzuka, Hideaki Hara

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins - inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.

Original languageEnglish
Pages (from-to)1782-1797
Number of pages16
JournalJournal of neurology
Issue number7
Publication statusPublished - 2013 Jul


  • Amyotrophic lateral sclerosis
  • Biomarker
  • Glutathione peroxidase 3
  • Inter-alpha-trypsin inhibitor heavy chain H4

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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