Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for AD, inducing oxidative stress to elevate intracellular iron, and analyze its co-localization with proteins using Magnetic Resonance Imaging (MRI), 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Western blot. We report three primary findings: 1) a significant loss in T2 signal over bilateral hippocampi of transgenic mice compared to the wild types (WT) by three months, corresponding to early disease and the ability of proteins to sequestration iron. Ability of rescue treatments to impede disease progression reflected as preserved T2 signal intensities over these areas throughout our study period of nine months. 2) Concentration of zinc and its dual role in the presence or absence of oxidative stress reflected as loss of 1H NMR T2 measurement showed that higher concentrations of zinc were neuro protective when there was an active oxidative stress inducing condition, but neurotoxic and promote oxidative damage in normal condition. And 3) Different strains of mice, according to their transgene, expressed various proteins associated with AD. However, these expressions were in accordance with our iron-hypothesis.
| Identifer | oai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-7944 |
| Date | 01 August 2017 |
| Creators | Adhikari, Rajan Deep |
| Publisher | BYU ScholarsArchive |
| Source Sets | Brigham Young University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Theses and Dissertations |
| Rights | http://lib.byu.edu/about/copyright/ |
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