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Synaptic density was estimated by positron emission tomography imaging with the radioligand [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty\u2010two participants with PSP\/CBD had a follow\u2010up [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J positron emission tomography scan after 1\u2009year. We calculated the annualized change in [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J nondisplaceable binding potential and correlated this with the change in clinical severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found significant annual synaptic loss within the frontal lobe (\u22123.5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03) and the right caudate (\u22123.9%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.47,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03) and cognition (Addenbrooke's Cognitive Examination\u2013Revised,\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u2009\u22120.62,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early\u2010phase clinical trials of disease\u2010modifying treatments. \u00a9 2023 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.29421","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T11:35:31Z","timestamp":1683891331000},"page":"1316-1326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [\n                    <scp>\n                      <sup>11<\/sup>\n                      C\n                    <\/scp>\n                    ]\n                    <scp>UCB\u2010J<\/scp>\n                    Positron Emission Tomography\u00a0Study"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-0882","authenticated-orcid":false,"given":"Negin","family":"Holland","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge, Cambridge Biomedical Campus  Cambridge United Kingdom"},{"name":"Cambridge University Hospitals NHS Foundation Trust  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Simon","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge, Cambridge Biomedical Campus  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Savulich","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Naessens","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge, Cambridge Biomedical Campus  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of 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