title: Selective neurotoxicity of COOH-terminal fragments of the beta-amyloid precursor protein.
abstract: The primary component of amyloid deposits found in the brains of patients with Alzheimer's disease is the beta-amyloid protein, a derivative of a much larger precursor protein (beta PP). We have previously reported that overexpression of carboxyl (COOH)-terminal fragments of beta PP from an integrated DNA construct leads to degeneration of neuronally differentiating mouse embryonic stem cells and that the neuronal degeneration is related to approximately 14- and 15-kDa COOH-terminal fragments of the precursor protein. We here demonstrate that these putative cytotoxic fragments contain intact beta-amyloid protein. When such transformed cell lines are treated with dimethyl sulfoxide to induce differentiation into muscle cells, however, the resulting muscle cells remain viable (as do control non-transformed cells), despite the production of comparable amounts of the 14- and 15-kDa fragments. These results are consistent with the hypothesis that particular COOH-terminal fragments of beta PP are amyloidogenic and neurotoxic.
authors.affiliation: Department of Pathology, University of Washington, Seattle 98195.
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: B
authors.initials: B
authors.lastname: Sopher
authors.forename: C E
authors.initials: CE
authors.lastname: Furlong
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.forename: N
authors.initials: N
authors.lastname: Dang
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D009218:Myosins / Q000096:biosynthesis; D009410:Nerve Degeneration / Q000502:physiology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D009218:Myosins; D004121:Dimethyl Sulfoxide