Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein

Haruka Sudo, Yuichi Hashimoto, Takako Niikura, Zongjun Shao, Takashi Yasukawa, Yuko Ito, Marina Yamada, Michihiro Hata, Takako Hiraki, Masaoki Kawasumi, Keisuke Kouyama, Ikuo Nishimoto

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Antibodies against APP, a precursor of Aβ deposited in Alzheimer’s disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Aβ mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Aβ40 and Aβ42 in the cultured media were undetectable by an assay capable of detecting 100 nM Aβ peptides. However, exogenously treated Aβ1.42 or Aβ1-43 required >3 μM to exert neurotoxicity, and 25 μM Aβ1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Aβ1-42, whereas serum attenuated toxicity by Aβ1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His657-Lys676, but not the Aβ1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Aβ.

Original languageEnglish
Pages (from-to)548-556
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume282
Issue number2
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Alzheimer’s disease
  • Amyloid precursor protein
  • Antibody-induced neuronal death
  • Aβ polypeptide
  • Cytoplasmic domain
  • Glutathione

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sudo, H., Hashimoto, Y., Niikura, T., Shao, Z., Yasukawa, T., Ito, Y., Yamada, M., Hata, M., Hiraki, T., Kawasumi, M., Kouyama, K., & Nishimoto, I. (2001). Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein. Biochemical and Biophysical Research Communications, 282(2), 548-556. https://doi.org/10.1006/bbrc.2001.4604