title: Transgenic mouse brain histopathology resembles early Alzheimer's disease.
abstract: Transgenic mice expressing the 751-amino acid form of the human amyloid precursor protein develop extracellular beta-amyloid protein (A beta)-immunoreactive deposits that increase in frequency with age. Here we show that the appearance and histological profile of deposits in the transgenic mice closely resemble those of preamyloid deposits in the brains of young adults with Down's syndrome, who presumably have the pathology of early-stage Alzheimer's disease. Specific monoclonal antibodies reveal that material in the deposits has the free carboxyl terminus of A beta 1-42, and that the deposits contain material which, by immunohistochemical analysis, apparently originates from the human beta-amyloid precursor protein (beta PP) transgene. In rare cases, the transgenic mouse brains contain several different histopathological characteristics of Alzheimer lesions. These features include dense A beta immunoreactivity which co-localizes with gliosis and with Alz50-immunoreactive structures resembling swollen boutons of dystrophic neurites. These observations demonstrate that the murine brain is capable of reproducing several typical features of Alzheimer histopathology.
authors.affiliation: Scios Nova, Mountain View, CA 94043.
authors.forename: L S
authors.initials: LS
authors.lastname: Higgins
authors.forename: D M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: J
authors.initials: J
authors.lastname: Rabin
authors.forename: W C
authors.initials: WC
authors.lastname: Mobley
authors.forename: B
authors.initials: B
authors.lastname: Cordell
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D013194:Staining and Labeling
chemical_list: D016229:Amyloid beta-Peptides