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Synaptic loss is an eminent feature of tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB\u2010J holds great potential for early diagnosis; however, there is a substantial knowledge gap in terms of the mechanism and the extent and nature of synaptic loss in PSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Here, we report an in\u2010depth\n                      <jats:italic>post mortem<\/jats:italic>\n                      validation and mechanistic study of UCB\u2010J in PSP and control brains using radioligand\/autoradiography binding studies, alongside biochemical correlation analyses of synaptic markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS AND DISCUSSION<\/jats:title>\n                    <jats:p>\n                      <jats:sup>3<\/jats:sup>\n                      H\u2010UCB\u2010J targeted synaptic vesicle protein 2A protein with high specificity and demonstrated a distinct interrelation with synaptic markers in PSP patients\u2019 brain regions. The loss of UCB\u2010J binding in the early and severely affected globus pallidus of PSP patients\u2019 brains revealed deficits of glutamate\/GABAergic synaptic terminals. Cortical and subcortical 4R tau load differentially impacted synaptic marker profiles across PSP patients, warranting further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>UCB\u2010J targeted synaptic vesicle protein 2A with high specificity in progressive supranuclear palsy (PSP) brains and demonstrated a conserved single nM binding site across different brain regions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>UCB\u2010J depicted prominent synaptic loss at the synaptosome levels and revealed deficits of glutamate\/GABAergic synaptic terminals in the early affected globus pallidus of PSP brains as compared to the control.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cortical and subcortical 4R tau load distinctly influenced synaptic markers profile across PSP patients and highlighted that presynaptic \u201cubiquitous\u201d markers individually might not be able to represent the complete state of synaptic deficits\/loss in PSP brains.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14409","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T07:02:08Z","timestamp":1734073328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>Post mortem<\/i>\n                    validation and mechanistic study of UCB\u2010J in progressive supranuclear palsy patients\u2019 brains"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-0966","authenticated-orcid":false,"given":"Miriam","family":"Scarpa","sequence":"first","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisavet","family":"Vallera","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Biology University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sira","family":"Ausell\u00e9\u2010Bosch","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Medical Sciences Faculty of Medicine University of Girona  Girona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa M.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buse Esra","family":"Mercan","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet  Stockholm Sweden"},{"name":"Faculty of Pharmacy Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avishek","family":"Roy","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Center for Alzheimer 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