A behavioural characterization of the 3xTg mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and two distinct forms of lesions in the brain: amyloid-beta plaques and neurofibrillary tangles (Oddo et al., 2003, Neuron, 39, 409-421). According to the Canadian Dementia Knowledge Translation Network (CDKTN) by 2011, over 100,000 new cases of AD will be diagnosed per year, and by 2031 close to 750,000 Canadians will have AD or a related disease. Transgenic mice have become a vital component in the advancement of research into possible causes, treatments, and cures for AD. However, until recently the majority of mouse models of AD focused solely on the development of amyloid-beta plaques; with mice expressing two transgenic mutations: an amyloid precursor protein (APP) mutation and a presenilin mutation, both linked to the development of plaque formation in familial AD (Morrissette et al., 2009, J Biol Chem, 284, 6033-6037). The recent development of the triple transgenic (3xTg) mouse model of AD is an attempt at providing a more complete animal model. In addition to both the APP and presenilin mutations, the 3xTg mice also possess a tau mutation which has been linked to the development of neurofibrillary tangles (Chin, 2010, Methods Mol Biol, 169-189). The neuropathology of the 3xTg mice closely resembles that which is seen in human patients of AD (Oddo et al., 2003, Neuron, 39, 409-421); but, to be a good model of the disease, the animals must show behavioural symptoms in addition to the neuropathology. To date, no studies have fully examined the behaviour of the 3xTg mice to observe whether or not these mice show progressive memory impairment and other symptoms associated with AD. The present study will thoroughly characterize the behaviour of the 3xTg mouse model of AD, using a comprehensive test battery designed to assess a variety of behaviours including: working memory, reference memory, long-term memory, anxiety, depression, general exploration, motor ability, and olfaction. Using a cross-sectional design, these behaviours will be assessed in mice aged 2-3 months, 6-7 months, 9-10 months, 12-13 months, and 15-16 months. Mapping out the behavioural profile of this realitvely new mouse model of AD will have significant effects on future research. By expressing neurofibrillary tangles in addition to amyloid-beta plaques, the 3xTg mouse model has already shown great potential as a more complete model of the disease, but it is crucial for researchers to understand how the behavioural symptoms develop and progress in order to effectively assess new treatments. Using the baseline behavioural data it will be possible for researchers to investigate whether new compounds not only influence neuropathology, but that they also influence cognitive decline and other behavioural symptoms in the transgenic mice.