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Alzheimer's Disease and Diabetes: A Transgenic Mouse Model in Behavior, MRI, and Cells

Alzheimer's disease (AD) is the most common form of dementia, afflicting almost 5 million patients in the US, and impacting millions more, financially, physically and emotionally. Coming in as the 6th leading cause of death in the US, and showing no signs of slowing its annually increasing rates, the world is in desperate need of improved understanding of the disease's multifaceted pathogenesis and progression, more accurate forms of detection and diagnosis, and more effective prevention and treatment. While many are focused on the noble pursuit of understanding the genetic contributions to the appearance of the pathological amyloid beta (Aβ)) plaques and tau tangles seen in AD, the majority of cases are not explained by genes or allele risk. Instead environmental, dietary and lifestyle contributors may be the key to understanding, diagnosing and treating this awful disease. Diet especially may impact the body's ability to regulate oxidative stress, which will cause damage within the cell and lead to further dysregulation of iron storage and metabolism. Iron storage is heavily monitored through cellular mechanisms, and the way in which the body reacts involves creation of the Aβ plaques and tau tangles as receptacles for the molecule it has deemed as the cause of the problem, iron. We have aptly named our theory, the Iron Hypothesis, and in the following document will outline the evidence for this hypothesis, and the experiments designed and performed to prove it.First, we aimed to examine the impacts that various treatments would have on a transgenic in-vivo model, examining the cohorts' behavior over several time points. We report a significant difference in the behavioral measures of time, distance, errors and failed trials in the radial arm maze existed between genotype, treatment and sex of the mice. Tissue of the experimental mice was collected, but will be processed and analyzed at a later date.Secondly, we aimed to examine the same cohorts of the in-vivo mouse model for minute anatomical changes that took place over the course of the aforementioned behavioral trials using novel MRI scanning sequences sensitive to the low levels of iron build up. We report significant differences in the UTE scan measures for our western diet treatment at TE's of 1.2ms. Additionally, further investigation and optimization of the protocol may be required to further expand the findings.

Identiferoai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-8460
Date01 August 2018
CreatorsSteed, Kevin Sage
PublisherBYU ScholarsArchive
Source SetsBrigham Young University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rightshttp://lib.byu.edu/about/copyright/

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