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Description
Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively

Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for 50-80% of dementia cases in the country. This disease is characterized by the deposition of extracellular plaques occurring in regions of the brain important for cognitive function. A primary component of these plaques is the amyloid-beta protein. While a natively unfolded protein, amyloid-beta can misfold and aggregate generating a variety of different species including numerous different soluble oligomeric species some of which are precursors to the neurofibrillary plaques. Various of the soluble amyloid-beta oligomeric species have been shown to be toxic to cells and their presence may correlate with progression of AD. Current treatment options target the dementia symptoms, but there is no effective cure or alternative to delay the progression of the disease once it occurs. Amyloid-beta aggregates show up many years before symptoms develop, so detection of various amyloid-beta aggregate species has great promise as an early biomarker for AD. Therefore reagents that can selectively identify key early oligomeric amyloid-beta species have value both as potential diagnostics for early detection of AD and as well as therapeutics that selectively target only the toxic amyloid-beta aggregate species. Earlier work in the lab includes development of several different single chain antibody fragments (scFvs) against different oligomeric amyloid-beta species. This includes isolation of C6 scFv against human AD brain derived oligomeric amyloid-beta (Kasturirangan et al., 2013). This thesis furthers research in this direction by improving the yields and investigating the specificity of modified C6 scFv as a diagnostic for AD. It is motivated by experiments reporting low yields of the C6 scFv. We also used the C6T scFv to characterize the variation in concentration of this particular oligomeric amyloid-beta species with age in a triple transgenic AD mouse model. We also show that C6T can be used to differentiate between post-mortem human AD, Parkinson's disease (PD) and healthy human brain samples. These results indicate that C6T has potential value as a diagnostic tool for early detection of AD.
ContributorsVenkataraman, Lalitha (Author) / Sierks, Michael (Thesis advisor) / Rege, Kaushal (Committee member) / Pauken, Christine (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Latino youth have substantially higher rates of obesity and T2D than their white peers. The higher prevalence of obesity and T2D among Latino youth places them at greater risk for cognitive dysfunction, an urgent and serious health threat to the United States. Exercise has been the cornerstone to combat the

Latino youth have substantially higher rates of obesity and T2D than their white peers. The higher prevalence of obesity and T2D among Latino youth places them at greater risk for cognitive dysfunction, an urgent and serious health threat to the United States. Exercise has been the cornerstone to combat the negative effects of obesity, diabetes and recent research also supports this effects for preventing cognitive dysfunction. A wealth of evidence suggests that a mediating mechanism linking exercise with brain health is BDNF, a cognitive biomarker that increases in the brain with exercise. BDNF is the most abundant neurotrophic factor that supports growth, survival and synaptic plasticity of neurons, all vital for cognitive function and brain health. The present study sought to investigate the effects of a 12-week lifestyle intervention of physical activity and lifestyle education on serum BDNF, in obese pre diabetic Latino youth.

A total of twelve obese pre diabetic Latino youth were selected from a larger RCT sample to be the focus for this analysis. After an overnight fast, a serum concentration was collected from all youth to be used for the BDNF analysis. In addition, the following cardio metabolic measures were also at taken at baseline and post intervention: Submaximal VO2max, medical and family history questionnaire, anthropometric, fasting glucose and a 2-hour oral glucose tolerance test (OGTT). A 12-weeks Lifestyle Intervention that involved a progressive moderate to high intensity exercise component and lifestyle education program did not significantly change serum BDNF levels in obese pre diabetic Latino youth. In conclusion, the variation of our serum BDNF results are highly speculative at this time, therefore the need for future investigations is crucial.
ContributorsBarraza, Estela (Author) / Shaibi, Gabriel Q. (Thesis advisor) / Swan, Pamela (Committee member) / Nanez, Jose E (Committee member) / Arizona State University (Publisher)
Created2016