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

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  • Christoph Scherfler, Hammersmith Hospital
  • ,
  • Naheed L. Khan
  • Nicola Pavese
  • Louise Eunson, University College Medical School
  • ,
  • Elizabeth Graham, University College Medical School
  • ,
  • Andrew J. Lees, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • Niall P. Quinn, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • Nicholas W. Wood, University College Medical School
  • ,
  • David J. Brooks
  • Paola P. Piccini, Hammersmith Hospital

To investigate striatal and cortical pre- and post-synaptic dopaminergic function in parkin-linked parkinsonism, 13 unrelated patients homozygous or compound heterozygous for parkin mutations were studied with [ 18F]dopa and [11C]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 [18F]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 [ 18F]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 [ 18F]dopa PET findings suggest that, compared with YOPD, parkin disease is associated with more severe and wide-spread 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.

Original languageEnglish
Pages (from-to)1332-1342
Number of pages11
Publication statusPublished - 1 Jun 2004
Externally publishedYes

    Research areas

  • [C]raclopride, [F]dopa, parkin gene, PET, SPM

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