{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:52:57Z","timestamp":1790376777669,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220258"],"award-info":[{"award-number":["220258"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","award":["SUAG\/092116768"],"award-info":[{"award-number":["SUAG\/092116768"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Synaptic loss is an early feature of neurodegenerative disease models, and is severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synaptic density in vivo. This study used [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J PET in participants with behavioral variant frontotemporal dementia (bvFTD), testing the hypothesis that synaptic loss is severe and related to clinical severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eleven participants with clinically probable bvFTD and 25 age\u2010 and sex\u2010matched healthy controls were included. Participants underwent dynamic [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J PET, structural magnetic resonance imaging, and a neuropsychological battery, including the revised Addenbrooke Cognitive Examination, and INECO frontal screening. General linear models compared [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J binding potential maps and gray matter volume between groups, and assessed associations between synaptic density and clinical severity in patients. Analyses were also performed using partial volume corrected [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J binding potential from regions of interest (ROIs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with bvFTD showed severe synaptic loss compared to controls. [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J binding was reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insular cortex, and medial temporal lobe. Synaptic loss in the frontal and cingulate regions correlated significantly with cognitive impairments. Synaptic loss was more severe than atrophy. Results from ROI\u2010based analyses mirrored the voxelwise results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      In accordance with preclinical models, and human postmortem evidence, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to severity. [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB\u2010J PET could support translational studies and experimental medicine strategies for new disease\u2010modifying treatments for neurodegeneration. ANN NEUROL 2023;93:142\u2013154\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26543","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T08:01:23Z","timestamp":1667376083000},"page":"142-154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Synaptic Loss in Frontotemporal Dementia Revealed by [\n                    <scp>\n                      <sup>11<\/sup>\n                      C\n                    <\/scp>\n                    ]\n                    <scp>UCB\u2010J Positron Emission Tomography<\/scp>"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"},{"name":"Cambridge University Hospitals National Health Service Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Simon","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Cope","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"},{"name":"Cambridge University Hospitals National Health Service Foundation Trust  Cambridge UK"},{"name":"Medical Research Council Cognition and Brain Sciences Unit University of Cambridge  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-0882","authenticated-orcid":false,"given":"Negin","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"},{"name":"Cambridge University Hospitals National Health Service Foundation Trust  Cambridge 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