Parkinson's disease (PD) is the most common degenerative hypokinetic movement disorder. Great strides have been made in the understanding of the pathophysiological mechanisms underlying the neurodegenerative processes in PD, prompting clinical trials of new therapies aimed at slowing or halting the progression of these diseases. To assess these new therapies, reliable in vivo markers of neuronal loss are needed. Currently available clinical measures of disease progression are relatively insensitive, and may not accurately reflect the extent of neuropathological change. Alternatively, quantitative biologically relevant brain imaging markers now exist which may be suitable as outcome measures for clinical trials. Specifically, we have developed three novel methods of assessing disease progression using positron emission tomography (PET): (1) The quantification of dopaminergic function using a radioligand which binds selectively to the dopamine transporter (DAT); (2) The quantitation of dynamic changes in brain-behavior relationships using regional blood flow activation and network analysis. The goal of the proposed project is to assess the extent to which neurochemical and functional PET imaging markers are sensitive to change in early stage PD, and to compare these measures to standard clinical induces of disease progression. To this end, we propose to extend our baseline functional imaging studies in early stage patients by carrying out longitudinal PET determinations of the neurochemical, metabolic, and functional activation markers over a three-year study. These studies will allow us to trace the temporal evolution of these imaging indices and to assess their relationship to standardized clinical measures of disease severity. We hypothesize that PET measures will be more sensitive to disease progression that clinical measures. If this is the case, clinical trials designed to assess potential neuroprotective therapies could require fewer patients and be completed in less time.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Columbia University (N.Y.)
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Guerreiro, Rita; Ross, Owen A; Kun-Rodrigues, Celia et al. (2018) Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol 17:64-74
Sun, Xiaotian; Aimé, Pascaline; Dai, David et al. (2018) Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease. Exp Neurol 303:95-107
Wu, Di; Klaw, Michelle C; Connors, Theresa et al. (2017) Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury. Mol Ther 25:2715-2726
Kun-Rodrigues, Celia; Ross, Owen A; Orme, Tatiana et al. (2017) Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. Neurobiol Aging 49:214.e13-214.e15
Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee et al. (2016) Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases. Neurobiol Aging 38:214.e7-214.e10
Wu, Di; Klaw, Michelle C; Kholodilov, Nikolai et al. (2016) Expressing Constitutively Active Rheb in Adult Dorsal Root Ganglion Neurons Enhances the Integration of Sensory Axons that Regenerate Across a Chondroitinase-Treated Dorsal Root Entry Zone Following Dorsal Root Crush. Front Mol Neurosci 9:49
Robakis, Daphne; Cortes, Etty; Clark, Lorraine N et al. (2016) The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease. J Neural Transm (Vienna) 123:583-8
Louis, Elan D; Clark, Lorraine; Ottman, Ruth (2016) Familial Aggregation and Co-Aggregation of Essential Tremor and Parkinson's Disease. Neuroepidemiology 46:31-6
Chung, Sun Young; Kishinevsky, Sarah; Mazzulli, Joseph R et al. (2016) Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and ?-Synuclein Accumulation. Stem Cell Reports 7:664-677
Pereira, Daniela B; Schmitz, Yvonne; Mészáros, József et al. (2016) Fluorescent false neurotransmitter reveals functionally silent dopamine vesicle clusters in the striatum. Nat Neurosci 19:578-86

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