Adenosine A_2A receptor availability in patients with early- and moderate-stage Parkinson's disease

Adenosine 2A (A_2A) receptors co-localize with dopamine D₂ receptors in striatopallidal medium spiny neurons of the indirect pathway. A_2A receptor activation in the striatum or pallidum decreases D₂ signaling. In contrast, A_2A receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A_2A receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A_2A receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A_2A receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias.

Brain MRI and PET with [¹¹C]TMSX radioligand, targeting A_2A receptors, was performed in 9 patients with early- and 9 with moderate-stage PD without dyskinesia and in 6 healthy controls. Distribution volume ratios (DVR) were calculated to assess specific [¹¹C]TMSX binding in caudate, putamen and pallidum.

A_2A receptor availability (DVR) was decreased in the bilateral caudate of early-stage PD patients when compared with healthy controls (P = 0.02). Conversely, DVR was increased bilaterally in the pallidum of moderate-stage PD patients compared to healthy controls (P = 0.03). Increased mean striatal DVR correlated with higher motor symptom severity ([Formula: see text] = 0.47, P = 0.02).

Our results imply regional and disease stage-dependent changes in A_2A receptor signaling in PD pathophysiology and in response to dopaminergic medication.