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

Purpose To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). Methods We quantified the cerebral binding potential (BPND) of the A(1)AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [F-18] 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 A(1)AR 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 A(1)AR 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 A(1)AR BPND and years to onset. Before onset of HD, the assumed annual rates of change of A(1)AR 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.