Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET

Dynamic [ ¹¹ C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinson's disease (PD). We investigated whether these complementary biomarkers could explain a higher percentage of motor symptom severity variation in PD and inform other PD-specific physiological alterations and symptomatology.

Binding potential ( BP _ND ) and relative perfusion ( R ₁ ) images were derived 30 PD and 30 controls imaged with [ ¹¹ C]UCB-J PET. A spatial covariance analysis was used on R ₁ to derive PDRP-a known metabolic network alteration in PD. Linear models related PD-motor symptom severity to PDRP expression and nigral synaptic losses. Next, whole-brain cluster analyses identified physiological correlates for PD-tremor severity, a prominent motor symptom that does not correlate with dopaminergic losses. Lastly, inter-individual regional correlation alterations in PD were examined for both BP _ND and R ₁ .

PDRP was identified from R ₁ , with higher expression in PD ( p =1.7×10 ^-5 , Cohen's d =1.2), and its expression correlated with MDS-UPDRS III ( r =0.57, p =0.0009). Combining PDRP expression scores with synaptic density in the substantia nigra explained 48% of the total variation in MDS-UPDRS Part III, twice as much as previously reported using nigral synaptic density alone. Two significant large clusters ( p _k <1×10 ^-6 ) were identified in the occipital-parietal areas where R ₁ was negatively correlated with tremor severity ( r ∼ -0.65, p <0.001). Extensive correlation alterations were observed in synaptic density (prominently involving pallidum) and perfusion (prominently involving thalamus).

Combining synaptic and perfusion outcomes for [ ¹¹ C]UCB-J PET explains more physiological alterations associated with PD.