{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:28:29Z","timestamp":1791941309929,"version":"4.3.4"},"reference-count":86,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"818","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n            Gray matter pathology, including the formation of cortical lesions, predicts progression in people with multiple sclerosis (PwMS). Here, we investigated whether positron emission tomography (PET) imaging using the synaptic vesicle protein 2A (SV2A)\u2013targeting radioligand [\n            <jats:sup>18<\/jats:sup>\n            F]UCB-H could help to detect and monitor synapse loss, an early feature of gray matter pathology in MS. First, we confirmed that SV2A is a suitable marker of synapse density in MS by analyzing SV2A mRNA and protein expression in cortical gray matter. We then used a mouse model of cortical MS pathology to demonstrate that SV2A-PET imaging can detect synapse loss in cortical lesions and that synapse densities measured by PET imaging correspond to the densities of genetically and immunohistochemically labeled synapses in the same lesions. Last, we performed SV2A-PET imaging in a total of 31 PwMS at different stages of the disease process, showing that PET imaging can detect synapse loss in cortical MS lesions in vivo. Moreover, we found that interhemispheric asymmetries in SV2A-PET tracer uptake can be leveraged to uncover further cortical alterations, the volume of which was more than 20-fold larger than the cortical lesion area detected by MRI. The extent of these PET-defined areas of cortical synapse pathology was larger in the progressive stage of the disease and correlated with the disability and cognitive performance of the same individuals. SV2A-PET imaging thus unmasked clinically relevant cortical pathology in MS thereby providing a promising tool to detect and monitor disease progression.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adt5585","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T17:59:39Z","timestamp":1759341579000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["SV2A-PET imaging uncovers cortical synapse loss in multiple sclerosis"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9811-1019","authenticated-orcid":true,"given":"Emily M.","family":"Ullrich Gavilanes","sequence":"first","affiliation":[{"name":"Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, 81377 Munich, Germany."},{"name":"Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6158-319X","authenticated-orcid":true,"given":"Laura M.","family":"Bartos","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, 81377 Munich, Germany."},{"name":"Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany."},{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-5557","authenticated-orcid":true,"given":"Jonathan A.","family":"Gernert","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, 81377 Munich, Germany."},{"name":"Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9605-4992","authenticated-orcid":true,"given":"Carla Ares","family":"Carral","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, 81377 Munich, Germany."},{"name":"Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4825-8624","authenticated-orcid":true,"given":"Diego","family":"Ruiz Navarro","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, 81377 Munich, Germany."},{"name":"Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, 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