Adenosine A2A receptor availability in patients with early- and moderate-stage Parkinson’s disease
Imran Waggan, Eero Rissanen, Jouni Tuisku, Juho Joutsa, Semi Helin, Riitta Parkkola, Juha O. Rinne, Laura Airas
Abstract
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 ( $$rho$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>rho</mml:mi> </mml:mrow> </mml:math> = 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.