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Science 28 July 1989:
Vol. 245. no. 4916, pp. 417 - 420
DOI: 10.1126/science.2474201
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Articles

Science, Vol 245, Issue 4916, 417-420
Copyright © 1989 by American Association for the Advancement of Science

articles

Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease

BA Yankner, LR Dawes, S Fisher, L Villa-Komaroff, ML Oster-Granite, and RL Neve

Department of Neurology, Harvard Medical School, Boston, MA.

Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer's disease. Whether amyloid itself contributes to the neurodegenerative process or is simply a by-product of that process is unknown. Pheochromocytoma (PC12) and fibroblast (NIH 3T3) cell lines were transfected with portions of the gene for the human amyloid precursor protein. Stable PC12 cell transfectants expressing a specific amyloid-containing fragment of the precursor protein gradually degenerated when induced to differentiate into neuronal cells with nerve growth factor. Conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against the amyloid polypeptide. Thus, a peptide derived from the amyloid precursor may be neurotoxic.


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