title: Behavioral abnormalities in APPSwe/PS1dE9 mouse model of AD-like pathology: comparative analysis across multiple behavioral domains.
abstract: Alzheimer's disease (AD) is characterized by dysfunction in cognitive and noncognitive domains with clinical diagnosis based on multiple neuropsychological tests. Here, we evaluated cognitive and noncognitive behaviors in 2 age cohorts (8 and 14 months at the start of the study) of APPSwe/PS1dE9 transgenic mice that model AD-like amyloidosis. We used a battery of tests that included fear-conditioned context and tone memories, swimming activity, and orientation to a proximal cue in a visible platform water maze test and burrowing and nest building activity. To compare the performance of mice across all tests, we used z-score normalization of data. The analyses revealed that the behavior of the transgenic mice was significantly compromised in cognitive as well as in noncognitive domains. Combining scores across multiple behavioral tests produced an integrated index characterizing the overall phenotypic abnormality in this model of AD-like amyloidosis. Assessing multiple behavioral domains provides a broader view of the breadth of impairments in multiple behavioral systems. Greater implementation of such approaches could enable reliable and clinically predictive evaluation of therapeutics in mouse models of amyloidosis.
authors.affiliation: Department of Neuroscience and Center for Translational Research in Neurodegenerative Diseases (CTRND), McKnight Brain Institute, University of Florida, Gainesville, FL, USA. Electronic address: cjanus@ufl.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Janus
authors.affiliation: Department of Neuroscience and Center for Translational Research in Neurodegenerative Diseases (CTRND), McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Abigail Y
authors.initials: AY
authors.lastname: Flores
authors.affiliation: Department of Neuroscience and Center for Translational Research in Neurodegenerative Diseases (CTRND), McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Guilian
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neuroscience and Center for Translational Research in Neurodegenerative Diseases (CTRND), McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000473:pathology*; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006801:Humans; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology; D001523:Mental Disorders / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009425:Nesting Behavior / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer's disease; Amyloid; Behavioral tests; Mouse models; Z-score normalization