Neurotoxicity of a Fragment of the Amyloid Precursor Associated with Alzheimer's Disease

• Published in: Science (American Association for the Advancement of Science) Vol. 245; no. 4916; pp. 417 - 420
• Main Authors: Yankner, Bruce A., Dawes, Linda R., Fisher, Shannon, Villa-Komaroff, Lydia, Oster-Granite, Mary Lou, Neve, Rachael L.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 28.07.1989; American Association for the Advancement of Science
• Subjects: 3T3 cells; Alzheimer Disease - etiology; Alzheimer Disease - pathology; Alzheimer's disease; Alzheimers disease; Amyloid - genetics; Amyloid - physiology; Amyloidosis; Amyloids; Antibodies; Biological and medical sciences; Blotting, Northern; Causes of; Cell Line; Cell lines; Complementary DNA; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fibroblasts; Gene Expression Regulation; Humans; Immunoblotting; Medical research; Medical sciences; Neuroglia; Neurology; Neurons; Neurons - pathology; Neurotoxic agents; Nucleic Acid Hybridization; PC12 cells; Peptides; Pheochromocytoma; Protein Precursors - genetics; Protein Precursors - physiology; Restriction Mapping; RNA; RNA - analysis; RNA - genetics; Transfection; Tumor Cells, Cultured; Human; 3T3»-Cell line; Alzheimer disease; Rodentia; Nerve growth factor; Northern blotting; Proteins; C terminal-Sequence; Vertebrata; Mammalia; Cell line; Transfection; Mouse; Neurotoxin; Immunoblotting assay; Amyloid; Degenerative disease; Biosynthesis precursor; Growth factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2474201

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.