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Thesis
Identifying Post-Translational Modifiers of Tau Protein as Clinically Meaningful Markers of Alzheimer's Disease
University of West Florida Libraries
Master of Science (MS), University of West Florida
2023
Abstract
Alzheimer’s disease (AD) is a neurodegenerative process that leads to significantcognitive disfunction and memory loss. It is characterized by the presence of neurofibrillary
tangles (NFTs) and amyloid-beta plaques (Aβ). These NFT’s are the result of the aggregation of
tau proteins in the neurons, leading to the axon shrinkage and neuronal dysfunction. During
normal aging or in the presence of disease, the tau protein undergoes various post-translational
modifications (PTMs). This study investigated the differences in these PTMs found between AD
and cognitively normal individuals, focusing on the ubiquitination of tau (Ub). To do so, a
constrained 7-mer (C7C) peptide phage library was panned to determine the presence or absence
of ubiquitinated tau for use as a biomarker for AD. After panning of the AD and control CSF,
phage was initially isolated selective toward tau isolated from AD subjects. Iterative panning of
this phage pool was conducted using a deubiquitinating enzyme (DUB). Panning with the DUB
resulted in phage selectively bound to AD tau in a ubiquitin-dependent manner. Overall, phage
display using the C7C library offered an easily measurable method of detection of tau proteins,
that distinguished AD subjects from controls. These findings are a potential biomarker and
detection method that could be used for potential early detection of AD in combination with
other AD biomarkers.
Details
- Title
- Identifying Post-Translational Modifiers of Tau Protein as Clinically Meaningful Markers of Alzheimer's Disease
- Resource Type
- Thesis
- Contributors
- Rodney P Guttmann (Committee Chair)Scott M Taylor (Committee Member)Peter Cavnar (Committee Member)
- Publisher
- University of West Florida Libraries
- Format
- pdf
- Number of pages
- 59
- Copyright
- © 2023 Kelvin James Williamson ALL RIGHTS RESERVED
- Identifiers
- 99380461696606600
- Academic Unit
- Biology; Hal Marcus College of Science and Engineering
- Language
- English
- Awarding Institution
- University of West Florida; Master of Science (MS)
- Theses and Dissertations
- Master of Science (MS), University of West Florida