title: A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease.
abstract: Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.
authors.affiliation: Department of Neuroscience, University of Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: K S
authors.initials: KS
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Knox
authors.forename: J
authors.initials: J
authors.lastname: Inglis
authors.forename: A
authors.initials: A
authors.lastname: Bernard
authors.forename: S J
authors.initials: SJ
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Justice
authors.forename: L
authors.initials: L
authors.lastname: McConlogue
authors.forename: D
authors.initials: D
authors.lastname: Games
authors.forename: S B
authors.initials: SB
authors.lastname: Freedman
authors.forename: R G
authors.initials: RG
authors.lastname: Morris
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D007124:Immunoenzyme Techniques; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid
chemical_list: D016229:Amyloid beta-Peptides