Antemortem Diagnostics in Prion Disease

  • Author / Creator
    Gushue, Danielle L
  • 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.

  • Subjects / Keywords
  • Graduation date
    Fall 2016
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. 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.