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

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

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).

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.

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.