[11C]Raclopride-PET studies of the Huntington's disease rate of progression: Relevance of the trinucleotide repeat length

Authors

  • Angelo Antonini MD,

    1. Movement Disorders Center and Functional Brain Imaging Laboratory, Department of Neurology, North Shore University Hospital, Manhasset NY
    2. PET Department, Paul Scherrer Institute, Villigen
    3. Movement Disorders Center, “Istituti Clinici di Perfezionamento,” Milan, Italy
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  • Dr Klaus L. Leenders MD,

    Corresponding author
    1. PET Department, Paul Scherrer Institute, Villigen
    2. Department of Neurology, University Hospital Zurich, Switzerland
    • PET Department, Paul Scherrer Institute, CH-5232 Villigen, Switzerland
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  • David Eidelberg MD

    1. Movement Disorders Center and Functional Brain Imaging Laboratory, Department of Neurology, North Shore University Hospital, Manhasset NY
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Abstract

We used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nontheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD.

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