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

Objective

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

Methods

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.

Results

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).

Conclusion

[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.