Longitudinal behavioral changes in the APP/PS1 transgenic Alzheimer's Disease model

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Abstract

HIGHLIGHTS

★ APP/PS1 mice were assessed longitudinally for coordination, activity & learning. ★ Motor coordination was normal in APP/PS1 mice and did not seem to decrease with age. ★ From 9 months of age until study end, open field activity of APP/PS1 mice was ↓. ★ Longer water maze latency and path length were related to ↑ floating/thigmotaxis. ★ Lack of age ↓ in water maze may relate to longitudinal testing & repeated experience.

The APP/PS1 double transgenic mouse is an Alzheimer's Disease-like model. However, cognitive deficits measured at one age do not necessarily indicate age-related progressions. Further, results of the most widely used behavioral assessment, water maze performance, are generally limited to 1–2 endpoints. Here, male APP/PS1 and noncarrier wildtypes (n = 11/group) were assessed at 7–15 months of age for water maze, open field, and motor coordination performance. Body weights and motor coordination were comparable for both groups throughout. Beginning at approximately 9 months of age, the transgenic group exhibited hypoactivity in the open field which continued throughout. Latency to locate the platform and swim path length were longer in the transgenic group; however, these appeared to be more related to increased floating and thigmotactic behavior and only partially related to a cognitive impairment. Age-related decrements in performance were not substantial; however, substantial plaque numbers were measured in six representative 16-month-old transgenic mice. The stability of water maze performance may be related to the longitudinal testing and repetitive experience, which previous research has demonstrated can confer beneficial effects on behavior and plaque deposition in transgenic Alzheimer's Disease models [1]. These results emphasize the importance of measuring multiple water maze endpoints and demonstrate the feasibility of longitudinal assessments in this model.

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