Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism

Brain. 2004 Jun;127(Pt 6):1332-42. doi: 10.1093/brain/awh150. Epub 2004 Apr 16.

Abstract

To investigate striatal and cortical pre- and postsynaptic dopaminergic function in parkin-linked parkinsonism, 13 unrelated patients homozygous or compound heterozygous for parkin mutations were studied with [(18)F]dopa and [(11)C]raclopride (RAC) PET. Data were compared with a young-onset Parkinson's disease (YOPD) cohort, matched for age, disease severity and duration, but negative for parkin mutations. Significant changes in [(18)F]dopa uptake and RAC binding potential (BP) were localized in striatum using regions of interest (ROIs) and throughout the entire brain volume with statistical parametric mapping (SPM). As expected, both YOPD and parkin patients showed significant decreases in striatal [(18)F]dopa uptake; however, in parkin patients, additional reductions in caudate and midbrain were localized with SPM. The RAC-BP was significantly decreased in striatal, thalamic and cortical areas (temporal, orbito-frontal and parietal cortex) in parkin compared with YOPD patients. Our [(18)F]dopa PET findings suggest that, compared with YOPD, parkin disease is associated with more severe and widespread presynaptic dopaminergic deficits. The global decreases in D2 binding found in parkin compared with YOPD patients could be a direct consequence of the parkin genetic defect itself or a greater susceptibility to receptor downregulation following long-term dopaminergic agent exposure. Cortical reductions in D2 binding may contribute to the behavioural problems reported in parkin patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dopamine / physiology*
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Presynaptic Terminals / physiology
  • Receptors, Dopamine D2 / metabolism
  • Tomography, Emission-Computed / methods
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Fluorine Radioisotopes
  • Receptors, Dopamine D2
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Dopamine