Grant: Project Grant

Alzheimer's disease (AD) affects approximately half a million Canadians, and is the most common form of age-related dementia. There continues to be an urgent need for the development of new therapies that slow or reverse the underlying disease process and relieve the symptoms of AD, and also of new animal models that mimic age-related disease progression and provide better predictive validity. The majority of currently used mouse models of AD exhibit pathological changes dependent on the overexpression of mutant human genes linked to early-onset, familial AD that account for only a small proportion of AD cases (1-2%). However, the study of lateonset/ age-related AD (98% of AD cases) has been hampered by the lack of such animal models. The research described in this proposal focusses on the use of HNE mice, a new, oxidative stress-based model of age-related cognitive impairment with AD-like pathologies. Validation of an age-related model of AD that complements current rodent models will allow greater insight into the pathogenesis and molecular/cellular mechanisms of AD. It will allow identification of targets for early intervention, and will be useful in assessing the efficacy of therapeutic agents for improving memory and for slowing, preventing, or reversing the synaptic failure and neurodegeneration associated with AD.