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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2014 | Original Article

Cross sectional PET study of cerebral adenosine A₁ receptors in premanifest and manifest Huntington’s disease

Authors: Andreas Matusch, Carsten Saft, David Elmenhorst, Peter H. Kraus, Ralf Gold, Hans-Peter Hartung, Andreas Bauer

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2014

Abstract

Purpose

To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington’s disease (HD).

Methods

We quantified the cerebral binding potential (BP _ND) of the A₁AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [¹⁸ F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36).

Results

Cerebral A₁AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p < .01, in the thalamus on average). Across stages a successive reduction of A₁AR BP_ND was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p < .01, in the caudatus and amygdala. There was a strong correlation between A₁AR BP _ND and years to onset. Before onset of HD, the assumed annual rates of change of A₁AR density were −1.2 % in the caudatus, −1.7 % in the thalamus and −3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively.

Conclusions

Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism.

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Title: Cross sectional PET study of cerebral adenosine A1 receptors in premanifest and manifest Huntington’s disease
Authors: Andreas Matusch
Carsten Saft
David Elmenhorst
Peter H. Kraus
Ralf Gold
Hans-Peter Hartung
Andreas Bauer
Publication date: 01-06-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-014-2724-8

At a glance: The STEP trials

Springer Medicine

Cross sectional PET study of cerebral adenosine A₁ receptors in premanifest and manifest Huntington’s disease

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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