Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides

DOI Web Site 74 Citations
  • Bruce A. Yankner
    Departnent of Neurology, Harvard Medical School, Boston, MA 02115 and the Children's Hospital, Boston, MA 02115.
  • Lawrence K. Duffy
    Department of Chemistry and Institute of Arctic Biology, University of Alaska, Fairbanks, AK 99775-0180.
  • Daniel A. Kirschner
    Departnent of Neurology, Harvard Medical School, Boston, MA 02115 and the Children's Hospital, Boston, MA 02115.

Abstract

<jats:p>The amyloid β protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid β protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid β protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid β protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid β protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid β protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.</jats:p>

Journal

  • Science

    Science 250 (4978), 279-282, 1990-10-12

    American Association for the Advancement of Science (AAAS)

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