title: A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment.
abstract: In the last decade, multiple lines of transgenic APP overexpressing mice have been created that recapitulate certain aspects of Alzheimer's disease (AD). However, none of the previously reported transgenic APP overexpressing rat models developed AD-like beta-amyloid (Abeta) deposits, or age-related learning and memory deficits. In the present study, we have characterized a transgenic rat model overexpressing transgenes with three, familial AD mutations (two in APP and one in PS1) that were developed by Flood et al. [Flood, D.G., et al., Abeta deposition in a transgenic rat model of Alzheimer's disease. Society for Neuroscience 2003, Washington, DC, 2003]. From the age of 9 months, these rats develop Abeta deposits in both diffuse and compact forms, with the latter being closely associated with activated microglia and reactive astrocytes. Impaired long-term potentiation (LTP) was revealed by electrophysiological recordings performed on hippocampal slices from rats at 7 months of age, which is 2 months before the appearance of amyloid plaques. The deficit in LTP was accompanied by impaired spatial learning and memory in the Morris water maze, which became more pronounced in transgenic rats of 13 months of age. For Tg rats of both ages, there was a trend for cognitive impairment to correlate with total Abeta42 levels in the hippocampus. The rat model therefore recapitulates AD-like amyloid pathology and cognitive impairment. The advantage of the rat model over the available mouse models is that rats provide better opportunities for advanced studies, such as serial CSF sampling, electrophysiology, neuroimaging, cell-based transplant manipulations, and complex behavioral testing.
authors.affiliation: Department of Pathology, Taub Institute for Research on Alzheimer's Disease, Columbia University, Black Building #5-513, 650 West 168th Street, New York, NY 10032, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Orozco
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.forename: Pavan
authors.initials: P
authors.lastname: Krishnamurthy
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Mathieu
authors.initials: M
authors.lastname: Herman
authors.forename: Helen
authors.initials: H
authors.lastname: Figueroa
authors.forename: W Haung
authors.initials: WH
authors.lastname: Yu
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.forename: Karen
authors.initials: K
authors.lastname: Duff
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019706:Excitatory Postsynaptic Potentials; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D053763:Presenilins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D053763:Presenilins