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 Vol 5: Using mice to model Alzheimers dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models.


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This article is from Frontiers in Genetics, volume 5.AbstractThe goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimers disease AD, and present a comprehensive analysis of the temporal progression of behavioral impairments in commonly used AD mouse models that contain mutations in amyloid precursor protein APP. We begin with a brief overview of the neuropathological changes seen in the AD brain and an outline of some of the clinical neuropsychological assessments used to measure cognitive deficits associated with the disease. This is followed by a critical assessment of behavioral tasks that are used in AD mice to model the cognitive changes seen in the human disease. Behavioral tests discussed include spatial memory tests Morris water maze MWM, radial arm water maze RAWM, Barnes maze, associative learning tasks passive avoidance, fear conditioning, alternation tasks Y-Maze-T-Maze, recognition memory tasks Novel Object Recognition, attentional tasks 3 and 5 choice serial reaction time, set-shifting tasks, and reversal learning tasks. We discuss the strengths and weaknesses of each of these behavioral tasks, and how they may correlate with clinical assessments in humans. Finally, the temporal progression of both cognitive and non-cognitive deficits in 10 AD mouse models PDAPP, TG2576, APP23, TgCRND8, J20, APP-PS1, TG2576 + PS1 M146L, APP-PS1 KI, 5×FAD, and 3×Tg-AD are discussed in detail. Mouse models of AD and the behavioral tasks used in conjunction with those models are immensely important in contributing to our knowledge of disease progression and are a useful tool to study AD pathophysiology and the resulting cognitive deficits. However, investigators need to be aware of the potential weaknesses of the available preclinical models in terms of their ability to model cognitive changes observed in human AD. It is our hope that this review will assist investigators in selecting an appropriate mouse model, and accompanying behavioral paradigms to investigate different aspects of AD pathology and disease progression.



Author: Webster, Scott J.; Bachstetter, Adam D.; Nelson, Peter T.; Schmitt, Frederick A.; Van Eldik, Linda J.

Source: https://archive.org/



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