title: [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold.
abstract: To estimate the threshold of nigrostriatal dysfunction required for symptomatic Parkinson's disease (PD), we employed [11C]RTI-32 and PET to study the dopamine transporter in striatal subdivisions of 11 L-dopa-naive patients with very early parkinsonism. As compared with the controls (N = 10), the PD group had on the side contralateral to the maximal clinical symptoms, significantly reduced binding in the posterior putamen (-56%) and anterior putamen (-28%), with the reduction in caudate (-12%) not significantly different. To the extent that dopamine transporter binding accurately reflects the number of nigrostriatal dopamine nerve terminals, these findings suggest that the clinical threshold for PD in the middle-age human is approximately 50% loss of dopaminergic innervation to the posterior putamen. Our data also suggest that damage to the putamen component of the striatum is sufficient for the clinical expression of PD.
authors.affiliation: Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Guttman
authors.forename: J
authors.initials: J
authors.lastname: Burkholder
authors.forename: S J
authors.initials: SJ
authors.lastname: Kish
authors.forename: D
authors.initials: D
authors.lastname: Hussey
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: DaSilva
authors.forename: S
authors.initials: S
authors.lastname: Houle
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis*; D018450:Disease Progression; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D013378:Substantia Nigra / Q000737:chemistry* / Q000503:physiopathology; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins