Vidal, RubenDeters, Kacie DanielleRisacher, Shannon L.Saykin, Andrew J.Farlow, MartinNho, KwangsikGao, Sujuan2017-08-172018-08-172017-06-29https://hdl.handle.net/1805/13851http://dx.doi.org/10.7912/C2/2068Indiana 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.en-USgeneticsneurodegenerationneuroimagingtauDissertation10.7912/C2RH1T