Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D 2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with 18 F-MNI-659 and 11 C-raclopride with correction for partial volume effect

Abstract Phosphodiesterase 10A enzyme ( PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10Ais expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D 2/3 receptors (D 2/3 R). The aim of this study was to examine the availability of PDE10Aenzyme in relation with age and gender and to compare those changes with those related to D 2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D 2/3 R and PDE10Aenzyme in the striatumand globus pallidus. Forty control subjects (20F/20M; age: 44±11y, age range 27–69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand18 F-MNI-659 and D 2/3 R radioligand11 C- raclopridewere used. The outcome measure was the binding potential( BP ND ) estimated with the two-tissue compartment model ( 18 F-MNI-659) and the simplified reference tissue model ( 11 C- raclopride) using the cerebellum as reference region. The PET data were corrected for partial volumeeffects. In the striatum, PDE10Aavailability showed a significant age-related decline that was larger compared to the age-related decline of D 2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10Aavailability was observed, whereas D 2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10Aenzyme was different from the distribution of D 2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10Aenzyme in the striatum. Moreover as result of the analysis, in the striatumfor both the molecular targets, we observed a gender effect with higher BP ND the female group.