{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:54:39Z","timestamp":1790913279115,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Neurology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["1R01NS124819"],"award-info":[{"award-number":["1R01NS124819"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/02g5p4n58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    Dynamic [\n                    <jats:sup>11<\/jats:sup>\n                    C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinson\u2019s 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.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Binding potential (\n                    <jats:italic>BP<\/jats:italic>\n                    <jats:sub>ND<\/jats:sub>\n                    ) and relative perfusion (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    ) images were derived 30 PD and 30 controls imaged with [\n                    <jats:sup>11<\/jats:sup>\n                    C]UCB-J PET. A spatial covariance analysis was used on\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    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\n                    <jats:italic>BP<\/jats:italic>\n                    <jats:sub>ND<\/jats:sub>\n                    and\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    .\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    PDRP was identified from\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    , with higher expression in PD (\n                    <jats:italic>p<\/jats:italic>\n                    =1.7\u00d710\n                    <jats:sup>-5<\/jats:sup>\n                    , Cohen\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    =1.2), and its expression correlated with MDS-UPDRS III (\n                    <jats:italic>r<\/jats:italic>\n                    =0.57,\n                    <jats:italic>p<\/jats:italic>\n                    =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 (\n                    <jats:italic>p<\/jats:italic>\n                    <jats:sub>k<\/jats:sub>\n                    &lt;1\u00d710\n                    <jats:sup>-6<\/jats:sup>\n                    ) were identified in the occipital-parietal areas where\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    was negatively correlated with tremor severity (\n                    <jats:italic>r<\/jats:italic>\n                    \u223c -0.65,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001). Extensive correlation alterations were observed in synaptic density (prominently involving pallidum) and perfusion (prominently involving thalamus).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Combining synaptic and perfusion outcomes for [\n                    <jats:sup>11<\/jats:sup>\n                    C]UCB-J PET explains more physiological alterations associated with PD.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.28.26364237","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:05:21Z","timestamp":1790726721000},"source":"Crossref","is-referenced-by-count":0,"title":["Alterations in relative perfusion and synaptic patterns in Parkinson\u2019s disease using dynamic SV2A PET"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9073-6270","authenticated-orcid":false,"given":"Praveen","family":"Honhar","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Sciences, Yale University, New Haven, CT, USA"},{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-8278","authenticated-orcid":false,"given":"Sule","family":"Tinaz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranak Ebrahimian","family":"Sadabad","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Dominique","family":"Gallezot","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Naganawa","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dias","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Ye","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabeel","family":"Nabulsi","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie E","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Comley","sequence":"additional","affiliation":[{"name":"AbbVie, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansel T","family":"Hillmer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Sciences, Yale University, New Haven, CT, USA"},{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd J","family":"Finnema","sequence":"additional","affiliation":[{"name":"AbbVie, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Matuskey","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, 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