Objective: We sought to investigate in vivo changes in A_2A receptor availability in cerebral white matter of PD patients and its association with gray matter atrophy.

Background: Atrophic changes in cerebral gray matter of patients with PD have been reported extensively. There is evidence suggesting an association between cortical gyrification changes and white matter abnormalities. Adenosine A_2A receptors have been shown to be upregulated in cerebral white matter and on reactive astrocytes in preclinical models of neurodegenerative diseases. However, changes in Adenosine A_2A receptor expression in white matter of patients with PD have not been explored.

Method: Eighteen patients with PD without dyskinesia and seven healthy controls were enrolled for this study. Brain MRI and dynamic PET scan was acquired with [¹¹C]TMSX radioligand which binds selectively to adenosine A_2A receptors. FreeSurfer software was used to segment cerebral gray and white matter structures. The resulting masks were used to calculate region specific volumes to derive distribution volume ratios (DVRs), after co-registration with PET images, for the quantification of specific [¹¹C]TMSX binding.

Results: We showed an increase in adenosine A_2A receptor availability in the frontal (P<0.001) and parietal (P<0.001) white matter of patients with PD as compared to healthy controls. A decrease in gray matter volume ratios was observed in frontal (P<0.01), parietal (P<0.001), temporal (P<0.01) and occipital (P<0.01) ROIs in patients with PD versus healthy controls. We also found an association between increased frontal white matter availability of A_2A receptors and lower frontal lobe volume ratio in patients with PD (R=−0.522, P=0.02).

Conclusion: Our results indicate that A_2A receptor-based signaling in frontal white matter is closely linked with neurodegenerative changes in the frontal gray matter of patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-increased-frontal-white-matter-a2a-receptor-availability-with-decreased-frontal-gray-matter-volume-in-patients-with-parkinsons-disease/