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Understanding the relationship between synaptic density and dopamine transporter availability in Parkinson’s disease

F. Ebrahimian Sadabad, T. Volpi, P. Honhar, S. Tinaz, M. Dias, T. Toyonaga, M. Naganawa, J. Gallezot, Y. Yang, W. Ibrahim, S. Cayir, R. Radhakrishnan, G. Angarita, S. Holmes, R. Comley, R. Carson, S. Finnema, D. Matuskey (New Haven, USA)

Meeting: 2025 International Congress

Keywords: Dopaminergic neurons, Parkinson’s, Positron emission tomography(PET)

Category: Parkinson's disease: Neuroimaging

Objective: To evaluate how disease duration in PD affects the coupling of DAT (18F-FE-PE2I) and SV2A density (11C-UCB-J) in the nigrostriatal regions (where both tracers yield measurable signals).

Background: The pathophysiology of Parkinson’s disease (PD) involves the degeneration of dopaminergic neurons in the substantia nigra (SN). 18F-FE-PE2I is a PET tracer targeting dopamine transporters (DAT), while 11C-UCB-J targets synaptic vesicle glycoprotein 2A (SV2A), a proxy of synaptic density. Both were found to be affected in PD, but the association between SV2A and DAT alterations has not been thoroughly investigated.

Method: 34 PD patients (16 women, 65.5±7.2 yo) and 13 healthy controls (HC) (7 women, 57.8±5.4 yo) underwent 18F-FE-PE2I and 11C-UCB-J PET imaging on separate days on a HRRT scanner. PD patients were stratified by disease duration into two subgroups: shorter-duration (<3 years, n=11), longer-duration (>6 years, n=13). PET data were partial-volume corrected (Muller-Gartner). Binding potentials (BPND) were quantified with SRTM2 (Reference regions: Cerebellum for 18F-FE-PE2I, centrum semiovale for 11C-UCB-J). Four gray-matter regions-of-interest (ROIs) were evaluated: Striatum (caudate, putamen, ventral striatum (VS)) and SN. Across-subject correlations between 18F-FE-PE2I and 11C-UCB-J BPND were assessed. The effects of age and between-scan interval, which were significantly different between groups, were regressed out.

Results: HC group showed significantly positive striatal correlations. Striatal correlations were mostly negative especially in the longer-duration PD group. Only the nigrostriatal correlations were significantly positive in the PD group. (Fig.1).

Conclusion: The coupling of DAT and SV2A density in the striatum and SN seems to be affected by PD and vary with disease duration. Studying the interplay between selective dopaminergic and overall presynaptic loss could help with early PD diagnosis and understanding of disease progression.

Figure 1

Figure 1

To cite this abstract in AMA style:

F. Ebrahimian Sadabad, T. Volpi, P. Honhar, S. Tinaz, M. Dias, T. Toyonaga, M. Naganawa, J. Gallezot, Y. Yang, W. Ibrahim, S. Cayir, R. Radhakrishnan, G. Angarita, S. Holmes, R. Comley, R. Carson, S. Finnema, D. Matuskey. Understanding the relationship between synaptic density and dopamine transporter availability in Parkinson’s disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/understanding-the-relationship-between-synaptic-density-and-dopamine-transporter-availability-in-parkinsons-disease/. Accessed October 21, 2026.
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