title: AβPP-overexpressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.
abstract: The current study examined behavioral and histological effects of amyloid-β (Aβ) protein precursor (AβPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg- offspring. Tg+ rats and Tg- littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg+ rats and Tg- littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg+ rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed-consecutive number schedule at 3 months old, Tg- littermates demonstrated a longer latency to learning the response rule than Tg+ rats; while this might seem paradoxical, it is consistent with the role of overexpression of AβPP in learning. Histological analyses revealed activated astrocytes in brains of Tg+ rats but not Tg- littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg+ rats but not Tg- littermates. Quantification of Aβ load in the brain at 22 months indicated high levels of Aβ38, Aβ40, and Aβ42 in the Tg+ rats. These data suggest this model might provide a valuable resource for AD research.
authors.affiliation: School of Psychology, Queen's University, Belfast, UK. e.ohare@qub.ac.uk
authors.forename: Eugene
authors.initials: E
authors.lastname: O'Hare
authors.forename: Tara
authors.initials: T
authors.lastname: Ardis
authors.forename: Deaglan
authors.initials: D
authors.lastname: Page
authors.forename: David I C
authors.initials: DI
authors.lastname: Scopes
authors.forename: Eun-Mee
authors.initials: EM
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D055647:Rats, Transgenic
chemical_list: D016564:Amyloid beta-Protein Precursor