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 Koyama, Ikuo Nishimoto

Research output: Contribution to journalArticle

28 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

Fingerprint

Amyloid beta-Protein Precursor
Anti-Idiotypic Antibodies
Antibodies
Toxicity
Cause of Death
Alzheimer Disease
Cell Death
Cell death
Neurons
Peptides
Assays
Brain
Serum

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein. / Sudo, Haruka; Hashimoto, Yuichi; Niikura, Takako; Shao, Zongjun; Yasukawa, Takashi; Ito, Yuko; Yamada, Marina; Hata, Michihiro; Hiraki, Takako; Kawasumi, Masaoki; Koyama, Keisuke; Nishimoto, Ikuo.

In: Biochemical and Biophysical Research Communications, Vol. 282, No. 2, 2001, p. 548-556.

Research output: Contribution to journalArticle

Sudo, H, Hashimoto, Y, Niikura, T, Shao, Z, Yasukawa, T, Ito, Y, Yamada, M, Hata, M, Hiraki, T, Kawasumi, M, Koyama, K & Nishimoto, I 2001, 'Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein', Biochemical and Biophysical Research Communications, vol. 282, no. 2, pp. 548-556. https://doi.org/10.1006/bbrc.2001.4604
Sudo, Haruka ; Hashimoto, Yuichi ; Niikura, Takako ; Shao, Zongjun ; Yasukawa, Takashi ; Ito, Yuko ; Yamada, Marina ; Hata, Michihiro ; Hiraki, Takako ; Kawasumi, Masaoki ; Koyama, Keisuke ; Nishimoto, Ikuo. / Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 282, No. 2. pp. 548-556.
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