title: Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein.
abstract: The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that beta-APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments.
authors.affiliation: Marion Merrell Dow Research Institute, Strasbourg, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Moran
authors.forename: L S
authors.initials: LS
authors.lastname: Higgins
authors.forename: B
authors.initials: B
authors.lastname: Cordell
authors.forename: P C
authors.initials: PC
authors.lastname: Moser
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016564:Amyloid beta-Protein Precursor