Adenosine A2A receptor availability in patients with early- and moderate-stage Parkinson’s disease

Abstract

Introduction: Adenosine 2A (A2A) receptors co-localize with dopamine D2receptors in striatopallidal medium spiny neurons of the indirect pathway. A2A receptor activation in the striatum or pallidum decreases D2signaling. In contrast, A2A receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A2A receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A2A receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A2A receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias. Methods: Brain MRI and PET with [11C]TMSX radioligand, targeting A2A 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. Results: A2A 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 (rho = 0.47, P = 0.02). Conclusion: Our results imply regional and disease stage-dependent changes in A2A receptor signaling in PD pathophysiology and in response to dopaminergic medication.