Alzheimer disease (AD) is the most common neurodegenerative disease, characterized by progressive memory loss and massive cell death in the cerebral cortex. A predominant view of the cause of AD is that the amyloid accumulation is the essential event leading to neurodegeneration. This hypothesis is supported by research on transgenic mice expressing familial mutations of the human amyloid precursor protein (APP) and presenilins. These animals reproduce key aspects of the disease, including amyloid plaques, deficits in cognitive tasks and abnormalities in the mechanisms of synaptic plasticity responsible for learning and memory. However, these mice rarely develop neurobibrillary tangles and exhibit little synaptic and neuronal loss, hallmarks of AD. In addition, these models of familial forms of AD might be less significant to study sporadic (non-familial) forms of AD, which represent about 95% of AD cases. We will examine the feasibility of using the rodent Octodon degus as a model to study sporadic forms of AD. Octodon degus, is a diurnal, visual and highly social rodent that naturally develop AD-like pathologies including amyloid plaques and neurobrillary tangles accumulation with age. Octodon degus also exhibit a marked age-related decline in the ability to discriminate novel from familiar objects, a working visual memory task. We hypothesize that the development of AD-like pathologies in O.degus alters synaptic plasticity and impairs visual memory. To test this hypothesis, we propose to determine in individual O. degus whether the degree of cognitive impairments correlates with deficits in synaptic plasticity and the Ab deposits. These investigations could establish an animal model for sporadic AD that will complement existing models of familial forms of the disease.
| Ardiles, Alvaro O; Tapia-Rojas, Cheril C; Mandal, Madhuchhanda et al. (2012) Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease. Proc Natl Acad Sci U S A 109:13835-40 |
| Braidy, Nady; Muñoz, Pablo; Palacios, Adrian G et al. (2012) Recent rodent models for Alzheimer's disease: clinical implications and basic research. J Neural Transm (Vienna) 119:173-95 |
