Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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- All Subjects: Alzheimer's Disease
Description
The apolipoprotein E (APOE) e4 genotype is the most prevalent known genetic risk factor for Alzheimer's disease (AD). In this paper, we examined the longitudinal effect of APOE e4 on hippocampal morphometry in Alzheimer's Disease Neuroimaging Initiative (ADNI). Generally, atrophy of hippocampus has more chance occurs in AD patients who carrying the APOE e4 allele than those who are APOE e4 noncarriers. Also, brain structure and function depend on APOE genotype not just for Alzheimer's disease patients but also in health elderly individuals, so APOE genotyping is considered critical in clinical trials of Alzheimer's disease. We used a large sample of elderly participants, with the help of a new automated surface registration system based on surface conformal parameterization with holomorphic 1-forms and surface fluid registration. In this system, we automatically segmented and constructed hippocampal surfaces from MR images at many different time points, such as 6 months, 1- and 2-year follow up. Between the two different hippocampal surfaces, we did the high-order correspondences, using a novel inverse consistent surface fluid registration method. At each time point, using Hotelling's T^2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes.
ContributorsLi, Bolun (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Liang, Jianming (Committee member) / Arizona State University (Publisher)
Created2015
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