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Recent in-vivo PET findings in early-onset depression and Alzheimer\u2019s Disease suggest that synaptic deficits contribute to the pathophysiology of these disorders and may therefore contribute to lower gray matter volume in late-life depression. Here, we investigate synaptic density in vivo for the first time in late-life depression using the synaptic vesicle glycoprotein 2A receptor radioligand <jats:sup>11<\/jats:sup>C-UCB-J. We included 24 currently depressed adults with late-life depression (73.0\u2009\u00b1\u20096.2 years, 16 female, geriatric depression scale = 19.5\u2009\u00b1\u20096.8) and 36 age- and gender-matched healthy controls (70.4\u2009\u00b1\u20096.2 years, 21 female, geriatric depression scale\u2009=\u20092.7\u2009\u00b1\u20092.9) that underwent simultaneous <jats:sup>11<\/jats:sup>C-UCB-J positron emission tomography (PET) and 3D T1- and T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. We used analyses of variance to test for <jats:sup>11<\/jats:sup>C-UCB-J binding and gray matter volumes differences in regions implicated in depression. The late-life depression group showed a trend in lower gray matter volumes in the hippocampus (<jats:italic>p<\/jats:italic>\u2009=\u20090.04), mesial temporal (<jats:italic>p<\/jats:italic>\u2009=\u20090.02) and prefrontal cortex (<jats:italic>p<\/jats:italic>\u2009=\u20090.02) compared to healthy control group without surviving correction for multiple comparison. However, no group differences in <jats:sup>11<\/jats:sup>C-UCB-J binding were found in these regions nor were any associations between <jats:sup>11<\/jats:sup>C-UCB-J and depressive symptoms. Our data suggests that, in contrast to Alzheimer\u2019s Disease, lower gray matter volume in late-life depression is not associated with synaptic density changes. From a therapeutic standpoint, preserved synaptic density in late-life depression may be an encouraging finding.<\/jats:p>","DOI":"10.1038\/s41398-024-02837-8","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T08:46:11Z","timestamp":1710405971000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Preliminary evidence for preserved synaptic density in late-life depression"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1559-4038","authenticated-orcid":false,"given":"Thomas","family":"Vande Casteele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-122X","authenticated-orcid":false,"given":"Maarten","family":"Laroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Van Cauwenberge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Koole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dupont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Sunaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-3195","authenticated-orcid":false,"given":"Jan","family":"Van den Stock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Bouckaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Van Laere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-4158","authenticated-orcid":false,"given":"Louise","family":"Emsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Vandenbulcke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"2837_CR1","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.biopsych.2006.09.006","volume":"60","author":"GS Alexopoulos","year":"2006","unstructured":"Alexopoulos GS. 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