Master of Science
Anatomy and Cell Biology
Dr. David Cechetto, Dr. Shawn Whitehead
Prior to beta-amyloid (Aβ) protein accumulation into plaques in Alzheimer’s disease (AD), neuroinflammation and oxidative stress have been shown to contribute to early cognitive decline. These cellular pathologies are coincident in stroke, which is considered a risk factor for AD. This study investigated the co-morbid effects of AD and stroke on behavioural and cellular pathology in two rodent models. Motor function, memory and microglial neuroinflammation were investigated in a stroke and Aβ injection model and mutant human amyloid precursor protein (APP) transgenic model with stroke. Injections of endothelin-1 into the right striatum were used to model stroke and AD was modelled through either intracerebroventricular Aβ25-35 injections or a transgenic rat that overproduces a mutated form of human APP. Furthermore, the effectiveness of a targeted antioxidant therapy (CAT-SKL) was investigated in the stroke and Aβ injection model. Memory deficits were present in both co-morbid conditions and CAT-SKL was able to ameliorate the memory deficit in the stroke and Aβ injection model. In the transgenic model, the co-morbid condition resulted in gait alterations. Levels of activated microglia in the infarct region were increased in the transgenic co-morbid condition. Exacerbation of activated microglia in the basal forebrain of the co-morbid stroke and Aβ injection model was observed and was attenuated by CAT-SKL treatment. The findings of this study demonstrate the co-morbid effects in the pathogenesis of AD pathologies. This study suggests that neuroinflammation plays a crucial role in AD and use of targeted therapies, such as CAT-SKL, should be the focus of future research on therapeutic strategies for AD.
Au, Jennifer L., "Co-Morbidity Of Alzheimer’s Disease And Stroke: Cognitive Deficits And Cellular Pathologies In Two Co-Morbid Animal Models" (2015). Electronic Thesis and Dissertation Repository. 3016.
Available for download on Wednesday, August 23, 2017