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From the MRC Clinical Sciences Centre and Division of Neuroscience (N.P., A.G., Y.F.T., F.T., D.J.B., P.P.), Faculty of Medicine, Imperial College, Hammersmith Hospital, London, and Centre for Brain Repair and Department of Neurology (A.K.H., R.A.B.), University of Cambridge, UK.
Address correspondence and reprint requests to Dr. P. Piccini, Hammersmith Hospital, DuCane Road, Cyclotron Bldg., W12 0NN, London, UK; e-mail: paola.piccini{at}csc.mrc.ac.uk
Background: Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process.
Methods: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [11C](R)-PK11195 PET, a marker of microglia activation, and [11C]raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function.
Results: In HD patients, a significant increase in striatal [11C](R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [11C]raclopride binding, the Unified Huntington’s Disease Rating Scale score, and the patients’ CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate.
Conclusions: These [11C](R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease (HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [11C](R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.
*These authors contributed equally to this article.
A. Gerhard was funded by the PDS UK (MAP 02/04). Y.F. Tai is funded by the Wellcome Trust. A.K. Ho was funded by the Medical Research Council.
Disclosure: The authors report no conflicts of interest.
Received June 30, 2005. Accepted in final form February 17, 2006.
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