Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET
- 1Yale University
Abstract
PurposeDynamic [11C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinsons 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.
MethodsBinding potential (BPND) and relative perfusion (R1) images were derived 30 PD and 30 controls imaged with [11C]UCB-J PET. A spatial covariance analysis was used on R1 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 BPND and R1.
ResultsPDRP was identified from R1, with higher expression in PD (p=1.7x10-5, Cohens 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 (pk<1x10-6) were identified in the occipital-parietal areas where R1 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).
ConclusionsCombining synaptic and perfusion outcomes for [11C]UCB-J PET explains more physiological alterations associated with PD.
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BibTeX
@misc{honhar2026alterations,
title = {{Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET}},
author = {P. Honhar and S. Tinaz and F. Ebrahimian Sadabad and J.-D. Gallezot and M. Naganawa and M. Dias and Y. Ye and H. Gao and N. Nabulsi and Y. Huang and S. E. Holmes and R. A. Comley and A. T. Hillmer and S. J. Finnema and D. Matuskey and R. E. Carson},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26364237},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26364237v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET
AU - P. Honhar
AU - S. Tinaz
AU - F. Ebrahimian Sadabad
AU - J.-D. Gallezot
AU - M. Naganawa
AU - M. Dias
AU - Y. Ye
AU - H. Gao
AU - N. Nabulsi
AU - Y. Huang
AU - S. E. Holmes
AU - R. A. Comley
AU - A. T. Hillmer
AU - S. J. Finnema
AU - D. Matuskey
AU - R. E. Carson
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26364237
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26364237v1
AB - PurposeDynamic [11C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinsons 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. MethodsBinding potential (BPND) and relative perfusion (R1) images were derived 30 PD and 30 controls imaged with [11C]UCB-J PET. A spatial covariance analysis was used on R1 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 BPND and R1. ResultsPDRP was identified from R1, with higher expression in PD (p=1.7x10-5, Cohens 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 (pk<1x10-6) were identified in the occipital-parietal areas where R1 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). ConclusionsCombining synaptic and perfusion outcomes for [11C]UCB-J PET explains more physiological alterations associated with PD.
ER -