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

Authors
  • Sudo, H
  • Hashimoto, Y
  • Niikura, T
  • Shao, Z
  • Yasukawa, T
  • Ito, Y
  • Yamada, M
  • Hata, M
  • Hiraki, T
  • Kawasumi, M
  • Kouyama, K
  • Nishimoto, I
Type
Published Article
Journal
Biochemical and biophysical research communications
Publication Date
Mar 30, 2001
Volume
282
Issue
2
Pages
548–556
Identifiers
PMID: 11401495
Source
Medline
License
Unknown

Abstract

Antibodies against APP, a precursor of Abeta deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Abeta mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Abeta40 and Abeta42 in the cultured media were undetectable by an assay capable of detecting 100 nM Abeta peptides. However, exogenously treated Abeta1-42 or Abeta1-43 required >3 microM to exert neurotoxicity, and 25 microM Abeta1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Abeta1-42, whereas serum attenuated toxicity by Abeta1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His(657)-Lys(676), but not the Abeta1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Abeta.

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