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 BPND 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.