Abstract
INTRODUCTION: Adenosine 2A (A(2A)) receptors co-localize with dopamine D(2 )receptors in striatopallidal medium spiny neurons of the indirect pathway. A(2A) receptor activation in the striatum or pallidum decreases D(2 )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. METHODS: Brain MRI and PET with [(11)C]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 [(11)C]TMSX binding in caudate, putamen and pallidum. RESULTS: 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). CONCLUSION: Our results imply regional and disease stage-dependent changes in A(2A) receptor signaling in PD pathophysiology and in response to dopaminergic medication.