Indiana University-Purdue University Indianapolis (IUPUI) / The pathway leading from soluble and monomeric to hyperphosphorylated,
insoluble and filamentous tau protein is at the center of many human neurodegenerative
diseases, collectively referred to as tauopathies, such as Alzheimer disease (AD). In this
report, we discuss the role of neuroimaging, genetics, and biomarkers in better
understanding the underlying brain changes in tauopathies. In Chapters 1 and 2, we
review current knowledge of tauopathies, the protein tau and FDG PET studies in AD. In
Chapter 3, we investigate glucose metabolism using [18F]FDG PET in a family with
multiple systems tauopathy with presenile dementia (MSTD), a primary tauopathy cause
by a mutation in MAPT. The results from this study suggest that mutation carriers have
lower [18F]FDG uptake, which may precede clinical onset. In Chapter 4, we assessed
brain glucose metabolism using [18F]Fluorodeoxyglucose (FDG) positron emission
tomography (PET) in individuals with Gerstmann–Sträussler–Scheinker Disease (GSS)
with the PRNP F198S mutation. The results from this study suggest hypometabolism in
the cerebellar and striatal regions, which may be preceded by hypermetabolism. This
chapter also evaluated if [11C]Pittsburgh Compound B (PiB) PET is capable of detecting
PrP-amyloid in GSS in individuals with the PRNP P102L and F198S mutations. The
results from this study suggest that [11C]PiB is not suitable for in vivo assessment of PrP
amyloid plaques in GSS. In Chapter 5, we examine a correlation between two peripheral
markers of axonal degeneration, plasma tau and neurofilament light (NFL), and MRI.
The results from this study suggest that plasma NFL may be a more specific marker for
neurodegeneration relative to plasma tau. In Chapter 6, we attempted to create a tau
biological network from gene and protein databases and literature search. We identified
over 150 genes that are related to tau protein or MAPT that are involved in different biological functions. Overall, the results of this report support the notion that using a
combination of techniques may help model progression of tau pathology. Future studies
may establish additional markers that may be used in combination with some of these
measures as tools for diagnosis and for the evaluation of treatment efficacy in
therapeutic trials.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/13851 |
| Date | 29 June 2017 |
| Creators | Deters, Kacie Danielle |
| Contributors | Vidal, Ruben, Risacher, Shannon L., Saykin, Andrew J., Farlow, Martin, Nho, Kwangsik, Gao, Sujuan |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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