The goal of this project is to elucidate some of the pharmacological changes in the central nervous system of patients with olivopontocerebellar atrophy (OPCA) and Alzheimer's disease with extrapyramidal signs (AD/EP). Positron emission tomography (PET) will be used to examine in the striatum the density of presynaptic monoaminergic terminals with [11C]dihydrotetrabenazine and postsynaptic D2 dopaminergic neurotransmitter receptors with [11C]raclopride. In patients with extrapyramidal (EP) motor disorders, the intensity of these disorders will be correlated with the findings in the PET studies. Two specific hypotheses will be tested. (l) In patients with OPCA, both sporadic and dominantly inherited forms, the density of striatal dopaminergic presynaptic terminals and of neurons containing D2 dopaminergic neurotransmitter receptors will be decreased in comparison with those in normal control subjects, and the degree of reduction will predict the future evolution of the disorder into clinically symptomatic multiple system atrophy (MSA). PET will be used to quantify the binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in these patients as compared to patients with fully developed MSA and normal control subjects with similar age and sex distributions. The evolution of the disease process in the OPCA patients will be observed clinically to detect those whose disorders evolve into MSA, then the PET studies of these cases obtained prior to the development of MSA will be compared with PET studies of patients with fully developed MSA, patients with OPCA who do not progress to MSA and normal control subjects, all with similar age and sex distributions. (2) In Alzheimer's disease (AD), EP motor disorders result at least in part from degeneration of striatal neurons containing D2 dopaminergic neurotransmitter receptors and not from degeneration of striatal dopaminergic presynaptic terminals, and the intensity of the extrapyramidal motor disorders is directly correlated with the degree of reduction of D2 dopaminergic receptors. PET will be used to quantify binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in patients with AD with and without extrapyramidal disorders in comparison to normal control subjects with similar age and sex distributions. The striatal binding studies will be correlated with the severity of the EP motor disorders as determined by quantitative clinical motor examinations.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Albin, Roger L; Fisher-Hubbard, Amanda; Shanmugasundaram, Krithika et al. (2015) Post-Mortem evaluation of amyloid-dopamine terminal positron emission tomography dementia classifications. Ann Neurol 78:824-30
Soileau, Michael J; Persad, Carol; Taylor, Jennifer et al. (2014) Caregiver burden in patients with Parkinson disease undergoing deep brain stimulation: an exploratory analysis. J Parkinsons Dis 4:517-21
Shao, Xia; Fawaz, Maria V; Jang, Keunsam et al. (2014) Ethanolic carbon-11 chemistry: the introduction of green radiochemistry. Appl Radiat Isot 89:125-9
Younes, Laurent; Ratnanather, J Tilak; Brown, Timothy et al. (2014) Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis. Hum Brain Mapp 35:792-809
Kilbourn, Michael R (2013) PET radioligands for the vesicular transporters for monoamines and acetylcholine. J Labelled Comp Radiopharm 56:167-71
Shao, Xia; Schnau, Paul L; Fawaz, Maria V et al. (2013) Enhanced radiosyntheses of [¹¹C]raclopride and [¹¹C]DASB using ethanolic loop chemistry. Nucl Med Biol 40:109-16
Bohnen, Nicolaas I; Müller, Martijn L T M (2013) In vivo neurochemical imaging of olfactory dysfunction in Parkinson's disease. J Neural Transm (Vienna) 120:571-6
Meisler, Miriam H; Grant, Adrienne E; Jones, Julie M et al. (2013) C9ORF72 expansion in a family with bipolar disorder. Bipolar Disord 15:326-32
Shao, Xia; Hoareau, Raphaël; Hockley, Brian G et al. (2011) Highlighting the Versatility of the Tracerlab Synthesis Modules. Part 1: Fully Automated Production of [F]Labelled Radiopharmaceuticals using a Tracerlab FX(FN). J Labelled Comp Radiopharm 54:292-307
Chen-Plotkin, Alice S; Martinez-Lage, Maria; Sleiman, Patrick M A et al. (2011) Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration. Arch Neurol 68:488-97

Showing the most recent 10 out of 27 publications