title: Transgenic animal models for Alzheimer's disease.
abstract: The neuropathology of Alzheimer's disease is characterized by the deposition of abnormal protein aggregates. The main constituent of the deposition is beta-amyloid protein. A seminal role of this protein is supported by the discovery of point mutations in the gene of its precursor protein in certain forms of familial Alzheimer's disease. In vitro (cultured neuronal cells), overexpression of the precursor protein or a part of the precursor leads to degeneration of neurons, suggesting neurotoxicity of its derivatives. At this time, all of the reported transgenic mice bearing DNA construct for the precursor or a part of the precursor, however, have not developed convincing pathological changes similar to what is observed in patients with Alzheimer's disease. This interesting discrepancy between in vitro and in vivo suggests suppressors in vivo which ameliorate beta-amyloid precursor protein derivative-mediated neurotoxicity.
authors.affiliation: Department of Pathology, University of Washington, Seattle 98195.
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: C E
authors.initials: CE
authors.lastname: Ogburn
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.forename: D D
authors.initials: DD
authors.lastname: Kunkel
authors.forename: C E
authors.initials: CE
authors.lastname: Furlong
authors.forename: S S
authors.initials: SS
authors.lastname: Deeb
authors.forename: D
authors.initials: D
authors.lastname: Nochlin
authors.forename: S M
authors.initials: SM
authors.lastname: Sumi
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D017354:Point Mutation
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009498:Neurotoxins; D010446:Peptide Fragments