Grant: Project Grant

About a quarter of middle aged Canadians are hypertensive and mounting evidence suggests these people are at a risk of exacerbated AD progression. The percentage of male/female hypertensive Canadians is equivalent in 45-65 aged individuals however more women develop late life AD suggesting that in women, hypertension could play a significant role in the etiology of AD. We will directly address the interaction between hypertension and AD progression in a transgenic rat model of AD, for the first time, by pharmacologically inducing mid-life hypertension and subsequently restoring normal blood pressure in these animals. In most people, elevated blood pressure is recognized and treated, thus our model more closely mimics life experience. Furthermore, we are using a state-of-the-art transgenic rat model of AD that shows a prodromal-disease phase followed by the full spectrum of age-dependent AD-like pathologies as well as loss of perception, thinking, reasoning and remembering. The power of combing these two models will allow us to address relationships previously out of reach. We will then use state-of-the-art in vivo neuroimaging, electrophysiology and pathological analyses to assess brain function at a cellular level in order to document the earliest stages of cognitive decline. Characterization of the brain injury in these animals relative to that of age-matched transgenic AD animals will provide crucial treatment targets for development of multifactorial therapies that address the combined pathology, and will thus enable improved outcomes for patients.