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- All Subjects: Alzheimer's Disease
Description
Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase.
ContributorsSuryadi, Vicky (Author) / Sierks, Michael (Thesis advisor) / Nielsen, David (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2014
Description
In our modern world the source of for many chemicals is to acquire and refine oil. This process is becoming an expensive to the environment and to human health. Alternative processes for acquiring the final product have been developed but still need work. One product that is valuable is butanol. The normal process for butanol production is very intensive but there is a method to produce butanol from bacteria. This process is better because it is more environmentally safe than using oil. One problem however is that when the bacteria produce too much butanol it reaches the toxicity limit and stops the production of butanol. In order to keep butanol from reaching the toxicity limit an adsorbent is used to remove the butanol without harming the bacteria. The adsorbent is a mesoporous carbon powder that allows the butanol to be adsorbed on it. This thesis explores different designs for a magnetic separation process to extract the carbon powder from the culture.
ContributorsChabra, Rohin (Author) / Nielsen, David (Thesis director) / Torres, Cesar (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Description
Alzheimer's disease (AD), which currently affects approximately 5.4 million Americans, is a type of dementia, which causes memory, cognitive, and behavioral problems. AD is among the top 10 leading causes of death in the United States, typically affecting people ages 65 and older. Beta-Amyloid (Aβ) is an Alzheimer's target protein, which starts as a single protein, but can misfold and bind to itself, forming larger chains and eventually fibrils and plaques of Aβ in the brain. Antibodies that bind to different regions and sizes of Aβ may prevent progression into a more toxic stage. The antibody worked with in this thesis, A4 scFv, binds to oligomeric Aβ. The objective of this antibody research is to optimize the production of functional antibodies, specifically A4, through modifications in the scFv growth process, in order to enhance the discovery of possible diagnostics and therapeutics for Alzheimer's disease. In order to produce functional A4 antibody, four complex sugars were tested in the E. Coli bacterial culture growth media that expresses the desired antibody. The sugars: sucrose, glucose, mannitol, and sorbitol were used in the growth process to improve the yield of functional antibody. Through the steps of growth, purification, and dialysis, the sugar sorbitol was found to provide the optimal results of ending functional antibody concentration. Once an ample amount of functional A4 scFv is produced, it can be used in assays as a biomarker for Alzheimer's disease.
ContributorsDolberg, Taylor Brianne (Author) / Sierks, Michael (Thesis director) / Nielsen, David (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Sustainability (Contributor)
Created2014-05
Description
With no known cure, Alzheimer's disease (AD) is the most common dementia, affecting more than 5.5 million Americans. Research has shown that women who undergo surgical menopause (i.e. removal of the ovaries) before the onset of natural menopause are at a greater risk for AD. It is hypothesized that this greater relative risk of developing AD is linked to ovarian hormone deprivation associated with surgical menopause. The purpose of these studies was to evaluate the behavioral changes that occur after a short-term (ST) and a long-term (LT) ovarian hormone deprivation in a mouse model of AD. Wildtype (Wt) or APP/PS1 (Tg) mutation mice underwent either a sham surgery or an ovariectomy (Ovx) surgery at three months of age. Study 1 consisted of a short-term cohort that was behaviorally tested one month following surgery on a battery of spatial memory tasks including, the Morris water maze, delayed matched-to-sample water maze, and visible platform task. Study 2 consisted of a long-term cohort that was behaviorally tested on the same cognitive battery three months following surgery. Results of Study 1 revealed that genotype interacted with surgical menopause status, such that after a short-term ovarian hormone deprivation, Ovx induced a genotype effect while Sham surgery did not. Results of Study 2 showed a similar pattern of effects, with a comparable interaction between genotypes and surgical menopause status. These findings indicate that the cognitive impact of ovarian hormone deprivation depends on AD-related genotype. Neuropathology evaluations in these mice will be done in the near future and will allow us to test relations between surgical menopause status, cognition, and AD-like neuropathology.
ContributorsPalmer, Justin M. (Author) / Bimonte-Nelson, Heather (Thesis director) / Oddo, Salvatore (Committee member) / Davis, Mary (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Alzheimer’s disease (AD) is an irreversible brain disorder that plagues millions of people with no current cure. Current clinical research is slowly advancing to more definitive treatments in hopes of reducing the effects of progressive cognitive and behavioral decline, but none so far can slow AD’s onset. A brain area known as the nucleus incertus (NI) was recently discovered to potentially impact AD because of its connections to brain targets that degenerate; however, the NI’s role is unknown. This goal of this experiment was to use a transgenic mouse model (APP/PS1) that expresses AD pathology slowly as found in humans, and to test the mice in a variety of cognitive and anxiety assessments. Mice of both sexes and two different ages were used, with the first being young adult before AD pathology manifests (around 3-4 months old), and the second being around the cusp of when AD pathology manifests (late adult, 8-10 months old). The mice were tested in a variety of cognitive tasks that included the novel object recognition (NOR), Morris water maze (MWM), and the object placement (OP), with the latter being the focus of my thesis. Anxiety measures were taken from the open field (OF) and elevated plus maze (EPM) with the visible platform (VP) used to ensure mice could perform on the rigorous MWM task. In the OP, we found an age effect, where the older mice were less likely to explore the moved object during the OP compared to the younger mice; motor ability was unlikely to explain this effect. We did not find any significant age by genotype effects. These findings indicate that cognitive impairment only just started to affect the older cohort, since OP impairment was found on one measure and not another. Other measures currently being quantified will be helpful in understanding this data, and to see whether learning, memory, and anxiety are affected.
ContributorsDapon, Bianca (Author) / Conrad, Cheryl (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2023-05
Description
There are currently no disease-modifying treatments to halt or attenuate the progression of Alzheimer’s disease (AD). Transgenic rodent models have provided researchers the ability to recapitulate particular pathological and symptomological events in disease progression. Complete reproduction of all features of AD in a rodent model has not been achieved, potentially lending to the inconclusive treatment results at the clinical level. Recently, the TgF344-AD transgenic rat model has started to be evaluated; however, it has not been well characterized in terms of its cognition, which is fundamental to understanding the trajectory of aging relative to pathology and learning and memory changes. Therefore, the aim of the current study was to identify cognitive outcomes at 6, 9, and 12 months of age in the TgF344-AD rat model. Sixty female transgenic (Tg) and wildtype (WT) rats were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. Results from the asymptotic phase of the water radial arm maze showed that the 6 mo-Tg animals had marginally impaired working memory compared to 6 mo-WT rats, and 12 mo-Tg rats had significantly impaired working memory compared to 12 mo-WT rats. The 9 mo-Tg animals did not demonstrate a significant difference in working memory errors compared to the 9 mo-WT animals. This pattern of impairment, wherein Tg animals made more working memory errors compared to WT animals at the 6 and 12 month time points, but not at the 9 month time point, may be indicative of an inflammatory response that proves helpful at incipient stages of disease progression but eventually leads to further cognitive impairment. These results provide insight into the potential earliest time point that prodromal cognitive symptoms of AD exist, and how they progress with aging. Brain tissue was collected at sacrifice for future analyses of pathology, which will be used to glean insight into the temporal progression of pathological and cognitive outcomes.
ContributorsBulen, Haidyn Leigh (Co-author) / Bulen, Haidyn (Co-author) / Bimonte-Nelson, Heather (Thesis director) / Presson, Clark (Committee member) / Conrad, Cheryl (Committee member) / Woner, Victoria (Committee member) / Peña, Veronica (Committee member) / School of International Letters and Cultures (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05