Developing and Employing a Behavioral Platform to Characterize a non-human Primate Model of Alzheimer's Disease

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Wither, Robert
Non-human Primates , Alzheimer's Disease , CANTAB , Actigraphy , Animal Models of Neurodegenerative Disease , Behavioral Platforms
Alzheimer’s disease (AD) is a devastating neurodegenerative disease and with shifting demographics, the number of affected individuals is estimated to increase dramatically. While a great deal of resources has been dedicated to researching new therapeutic strategies, most of the promising rodent results have failed to translate to clinical success, suggesting that perhaps inter-species differences represent a major obstacle. As such, there is an urgent need for more translationally relevant animal models of disease, and non-human primates (NHPs), a phylogenetically closer species, are promising candidates. In order to validate these NHP models of disease, it requires demonstration that similar behavioral and cognitive deficits are observed in both the model and the disease it seeks to emulate. To maximize the translational value of these models, the same neural correlates and processes underlying the behavioral deficits should be measured, which necessitates using tasks and experimental procedures that have cross-species translational validity. In this thesis we detail a collection of 4 studies that describe a behavioral testing platform for NHP models of neurodegenerative diseases. The first 2 studies describe the training, performance, and response time profiles of control NHPs on a series of cognitive tasks included in the Cambridge neuropsychological testing automated battery (CANTAB). The third study examines the use of the actical, a 3-D accelerometer, to characterize the daily activity patterns of a colony of control NHPs. Additionally, this study describes a number of environmental factors that influence and disrupt normal behavioral patterning in NHPs. In the final study, we used this developed behavioral platform of CANTAB and actigaphy/accelerometry approaches to characterize the effects of intracerebroventricular injected amyloid-beta oligomers (AβOs) as an NHP model of AD. Using the CANTAB, we noted that AβO-injected NHPs displayed decreased task performance and lengthened response times suggesting impaired spatial, object- based, and associative working memory capabilities. Using accelerometry, we also found that global activity levels were diminished in AβO-injected NHPs, but that proper circadian patterning was still intact.
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