Presynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease

To investigate the relationship of synaptic loss with glucose metabolism and dopaminergic transporters in Parkinson’s disease (PD) patients.

A total of 16 patients with PD and 11 age-matched healthy controls underwent positron emission tomography (PET) with the tracers [¹⁸F]SynVesT-1, a ligand for the presynaptic terminal marker synaptic vesicle protein 2 A (SV2A), and FDG. PD patients also underwent PET with the dopamine transporter (DAT) ligand [18F]FP-CIT. The difference in synaptic density between PD patients and age-matched normal controls(NCs) was determined in the selected regions of interest, and the correlations of the [¹⁸F]SynVesT-1 PET SUVRs with [¹⁸F]FP-CIT PET SUVRs and [¹⁸F]FDG PET SUVRs were evaluated.

Compared with that in the NC group, the synaptic density in the caudate region was significantly lower in the PD group (SUVR: 2.51 ± 0.36 vs. 3.18 ± 0.32, p < 0.001), especially in the pre-commissural caudate and post-commissural caudate (SUVR: 2.42 ± 0.29 vs. 2.63 ± 0.32, p < 0.01; 0.76 ± 0.31 vs. 0.97 ± 0.33, p < 0.001). A reduced synaptic density was significantly correlated with DAT (r = 0.61, p < 0.001) and glucose metabolism (r = 0.73, p < 0.001) in the post-commissural caudate. In the post-commissural regions of the caudate, there was a partial mediating effect of synaptic density on the relationship between glucose metabolism and DAT availability (indirect effect: β₄ = 0.039, p = 0.024).

[¹⁸F]SynVesT-1 binds specifically to SV2A, reflecting synaptic density, and there is a positive correlation metabolic pattern related to the changes reflected by [¹⁸F]SynVesT-1 and [¹⁸F]FDG.