Adenosine A 2A receptor availability in patients with early- and moderate-stage Parkinson's disease

• Published in: Journal of neurology 2023-01, Vol.270 (1), p.300
• Main Authors: Waggan, Imran, Rissanen, Eero, Tuisku, Jouni, Joutsa, Juho, Helin, Semi, Parkkola, Riitta, Rinne, Juha O, Airas, Laura
• Format: Article
• Language: English
• Subjects: Adenosine - therapeutic use; Dyskinesias - drug therapy; Humans; Levodopa - therapeutic use; Parkinson Disease - drug therapy; Receptor, Adenosine A2A - metabolism; Receptor, Adenosine A2A - therapeutic use
• ISSN: 1432-1459
• DOI: 10.1007/s00415-022-11342-1

Adenosine 2A (A ) receptors co-localize with dopamine D receptors in striatopallidal medium spiny neurons of the indirect pathway. A  receptor activation in the striatum or pallidum decreases D signaling. In contrast, A  receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A  receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A  receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A  receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias. Brain MRI and PET with [ C]TMSX radioligand, targeting A  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 [ C]TMSX binding in caudate, putamen and pallidum. A  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  receptor signaling in PD pathophysiology and in response to dopaminergic medication.