Brooks, DavidRamlackhansingh, AnilAnilRamlackhansingh2015-06-112015-06-112013-03almahttp://hdl.handle.net/10044/1/23658Summary of Objectives: Neurodegeneration is an important pathological component hallmark of many neurological illnesses. Effective management demands a greater understanding of the changes taking place at a neuronal level. In this thesis I have investigated the biochemical changes at the cellular level in four conditions associated with neurodegneration – traumatic brain injury (TBI), prion disease, posterior cortical atrophy (PCA) and Parkinson’s disease (PD). Positron Emission Tomography (PET) scanning was my main investigative tool. Each condition was investigated using up to four different radioactive PET ligands: 1. [11C]-PIB, to measure beta amyloid load and detect other β sheet folded proteins in the brain, 2. [11C]-PK11195, to quantitate microglia activation in the brain, 3. [18F]-FDG, to investigate changes in the pattern of cerebral glucose metabolism, and 4. [11C]-SCH442416, used specifically in PD to investigate changes in striatal adenosine 2A receptor concentrations. Subjects also underwent MRI scanning. Neuropsychological assessments were conducted on TBI subjects in an attempt to correlate any PET changes with clinical findings. Summary of Results: Subjects with chronic TBI demonstrated increased [11C]-PK11195 uptake in subcortical structures including the thalamus and putamen distant from the original focal brain lesion. Processing speed in TBI subjects was positively correlated with thalamic [11C]-PK11195 uptake. [11C]-PIB PET did not show a significant increase in signal compatible with amyloid deposition following TBI. In prion disease there was no increased uptake of [11C]-PIB although prion protein form beta pleated sheets. In PCA there is reduced parieto-occpital [18F]-FDG signal despite the [11C]-PIB pattern of binding being more typical of Alzheimer’s Disease. Adenosine 2A receptor availability was significantly raised in the striatum of PD patients with levodopa induced dyskinesias. These studies suggest that amyloid plaque deposition may not be the driving force of neuronal damage while microglial deactivation may play a leading role in driving disease. My work also suggests there is deregulation of adenosine transmission in dyskinetic PD and that A2A adenosine blockade may have therapeutic potential.Thesis or dissertationhttps://doi.org/10.25560/23658