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J Nucl Med. 2014; 55 (Supplement 1):32
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Neurosciences

Brain Imaging Council Young Investigator Award Symposium

Brain phosphodiesterase 10A (PDE-10A) density in early premanifest HD gene carriers

Flavia Niccolini1, Tiago Reis Marques2, Salman Haider3, Graham Searle4, Sridhar Natesan2, Shitij Kapur2, Eugenii Rabiner4, Roger Gunn4, Sarah Tabrizi3 and Marios Politis5

1 Medicine, Imperial College London, London, United Kingdom 2 Institute of Psychiatry, King’s College London, London, United Kingdom 3 Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom 4 Imanova, London, United Kingdom 5 Neurodegeneration Imaging Group, Department of Clinical Neuroscience, King's College London, London, United Kingdom

Abstract No. 32

Objectives: Huntington’s disease (HD) is a progressive neurodegenerative autosomal dominant movement disorder. PDE-10A is an enzyme highly expressed in the striatal medium spiny neurons, where it regulates both cAMP and cGMP signalling cascades, mediating the striatal outputs and having a central role in the control of movement. The objective of this study was to evaluate the in vivo availability of PDE-10A in the brain of early premanifest HD gene carriers, using [11C]-IMA-107 positron emission tomography (PET).

Methods: We have quantified the availability of PDE10 in the brains of 7 premanifest HD gene carriers (4 males; CAG range: 40-44; mean disease-burden score = 265). The mean predicted symptom onset for the group was 24 years. PET images were anatomically coregistered and resliced to the corresponding volumetric T1-weighted MRI using the Mutual Information Registration algorithm in SPM8. Regions-of-interest (ROIs) were delineated manually using ANALYZE 11.Regional [11C]-IMA-107 BPND were generated using a simplified reference tissue model (SRTM) with the cerebellum as the reference region.

Results: Premanifest HD gene carriers had significantly lower mean [11C]-IMA-107 BPND than healthy volunteers in the caudate (27.7%; p = 0.003), putamen (23.7%; p = 0.004) and globus pallidus (15.4%; p = 0.004). In the substantia nigra the HD patients BPND was higher than that of healthy volunteers (18.5%; p>0.05).

Conclusions: Our findings suggest that PDE-10A is dysregulated in HD gene carriers, decades before the appearance of clinical symptoms. [11C]-IMA-107 PET may provide a valuable tool to understand the pathophysiology of HD, and monitor both disease progression and the response to treatment.

Research Support: NIHR Biomedical Research Centre





This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Niccolini, F.
Right arrow Articles by Politis, M.
PubMed
Right arrow Articles by Niccolini, F.
Right arrow Articles by Politis, M.