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Permanent link (DOI): https://doi.org/10.7939/R34F1MV51

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Antemortem Diagnostics in Prion Disease Open Access

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Other title
Subject/Keyword
Prion
Biomarker
CJD
14-3-3
Proteomics
Antemortem
Preclinical
Neurodegeneration
CSF
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Gushue, Danielle L
Supervisor and department
Judd Aiken (Agricultural, Food, and Nutritional Science)
Examining committee member and department
Debbie McKenzie (Biological Sciences
Valerie Sim (Medicine - Division of Neurology)
Leluo Guan (Agricultural, Food, and Nutritional Science)
Department
Department of Agricultural, Food, and Nutritional Science
Specialization
Animal Science
Date accepted
2016-09-27T11:54:28Z
Graduation date
2016-06:Fall 2016
Degree
Master of Science
Degree level
Master's
Abstract
Antemortem identification of Creutzfeldt-Jakob disease (CJD) patients is initially based upon clinical presentation of the disease. Symptoms are assessed in combination with results from cerebrospinal fluid (CSF) analysis, electroencephalography (EEG), magnetic resonance imaging (MRI), and real-time quaking-induced conversion assay (RT-QuIC) for diagnostic purposes. Inconsistencies in sensitivities and specificities of prion disease biomarker abundance in CSF have been described and a lack of standardization for how biomarker levels are measured has been identified. Clinical presentation and progression of human prion disease is variable due to factors such as prion protein genotype, prion strain and other undefined genetic or environmental contributions, which may confound the appearance or abundance of biomarkers. By contrast, prion disease in laboratory rodents follows a defined disease course as the infection route and time, prion strain, genotype and environmental conditions are all controlled. We adapted prion disease to rats, facilitating a proteomic approach to a bioavailable fluid, CSF, at preclinical and clinical disease stages. This contrasts with human CJD samples, which are generally only available at clinical stage. The rat CSF proteome was compared between infected rats and age-matched controls through mass spectrometry. A number of proteins up-regulated and/or specific to prion disease were identified. These proteins included known CJD biomarkers, 14-3-3 and neuron-specific enolase (NSE), demonstrating the utility of using rat prion disease for biomarker identification. The objective of this study is to validate the use of these markers at clinical stage and to define the pre-clinical abundance, as the utility of 14-3-3 and NSE at pre-clinical disease stages are not well characterized. Tracking the progression of prion infection in rats will allow us to further define prion disease neurodegeneration and will allow for identification of novel biomarker candidates that may offer greater utility at both pre-clinical and clinical stages as diagnostic and prognostic tools.
Language
English
DOI
doi:10.7939/R34F1MV51
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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