title: Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer's disease.
abstract: To determine if early cognitive sensorimotor deficits exist in APP(SW) transgenic mice overexpressing human amyloid precursor protein (APP). Tg+ and Tg- animals at both 3 and 9 months of age (3M and 9M, respectively) were evaluated in a comprehensive battery of measures. The performance of all Tg+ mice at both ages was no different from all Tg- controls in Y-maze alternations, water maze acquisition, passive avoidance, and active avoidance testing. By contrast, results from other tasks revealed substantive cognitive deficits in Tg+ mice that were usually gender-dependent and sometimes progressive in nature. Between 3M and 9M, a progressive impairment was observed in circular platform performance by Tg+ males, as was a progressive deficit in visible platform testing for all Tg+ animals. Other transgenic effects included both impaired water maze retention and circular platform performance in 3M Tg+ females; this later effect was responsible for an overall (males + females) Tg+ deficit in circular platform performance at 3M. Sensorimotor testing revealed several Tg+ effects, most notably an increased activity of Tg+ males in both open field and Y-maze at 3M. Significant correlations between a number of behavioral measures were observed, although factor analysis suggests that each task measured components of sensorimotor/cognitive function not measured by other tasks. Finally, Tg+ mice had lower survivability than Tg- animals through 9M (85 vs. 96%). In summary, these results demonstrate the presence of gender-related and progressive cognitive deficits in APP(SW) transgenic mice at a relatively early age (i.e., prior to overt, beta-amyloid deposition in the brain), suggesting a pathophysiologic role for elevated levels of 'soluble' beta-amyloid in such impairments.
authors.affiliation: Alzheimer's Research Laboratory, Department of Biology, University of South Florida, Tampa 33620, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: King
authors.forename: G W
authors.initials: GW
authors.lastname: Arendash
authors.forename: F
authors.initials: F
authors.lastname: Crawford
authors.forename: T
authors.initials: T
authors.lastname: Sterk
authors.forename: J
authors.initials: J
authors.lastname: Menendez
authors.forename: M J
authors.initials: MJ
authors.lastname: Mullan
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics / Q000523:psychology*; D005106:Exploratory Behavior; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D058225:Plaque, Amyloid / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology; D012727:Sex Characteristics; D016019:Survival Analysis
chemical_list: D016564:Amyloid beta-Protein Precursor