Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer’s disease

Abstract

Recently, interest in the rat as an animal model of Alzheimer’s disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of Aβ deposition, predominantly in cerebrovascular blood vessels, after 15 months of age. Here we show that by the age of 9 months, that is long before the appearance of Aβ deposits, the Tg6590 rats exhibit deficits in the Morris water maze spatial navigation task and altered spontaneous behaviour in the open-field test. The levels of soluble Aβ were elevated both in the hippocampus and cortex of transgenic animals. Magnetic resonance imaging showed no major changes in the brains of transgenic animals, although they tended to have enlarged lateral ventricles when compared to control animals. The Tg6590 transgenic rat line should prove a suitable model of early AD for advanced studies including serial cerebrospinal fluid sampling, electrophysiology, neuroimaging or complex behavioural testing.

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice

“…Several new mouse models are now available with cognitive impairment induced by pharmacologic, toxicological, and genetic methods [45]. Although these animal models have been successfully applied to investigate memory disorders, such as Alzheimer’s disease [46] and PD [47], the age-related cognitive decline is not fully explained using these artificially-induced models. Although a relatively longer time and additional resources are needed in order to use naturally-aged mice, we employed naturally-aged mice to recapitulate the aging systemic milieu [48] and subsequent response to TEE supplementation.…”

Rodent models in neuroscience research: is it a rat race?

“…A key challenge that has emerged in using rats to model AD is that transgenic rats do not seem to develop AD-like plaques. For instance, the Tg6590 rat model (based on a mutation observed in Swedish cohorts of AD) does not display mature plaques (Kloskowska et al, 2010), whereas the mouse equivalent (Tg2576) shows substantial plaque formation (Hsiao et al, 1996). Intriguingly, cognitive deficits are present in both rat and mouse models, calling into question the causal relationship between plaques and dementia.…”

The rat as an animal model of Alzheimer's disease

“…These rats developed mild extracellular Aβ immunoreactivity but no compact mature amyloid deposits. The level Ap42 and Aβ40 are increased to a similar extent as would be expected due to the mutation used [94]. The levels of both Aβ species are increased 65% in hippocampus and 40% in cortex of 11‐month‐old animals.…”

“…The levels of both Aβ species are increased 65% in hippocampus and 40% in cortex of 11‐month‐old animals. The Tg6590 rats display learning and memory deficits in the Morris water maze at the age of 9 months and altered spontaneous behaviour measured in open‐field [94]. As in several APP mouse models, these behavioural changes are seen prior to the appearance of any amyloid depositions.…”