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We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Twenty\u2010one participants with early AD and 7 cognitively normal (CN) individuals underwent [<jats:sup>11<\/jats:sup>C]UCB\u2010J PET. We used a novel enzyme\u2010linked immunosorbent assay (ELISA) to measure CSF SV2A. Other synaptic and axonal proteins were also measured in CSF.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>CSF SV2A was lower in AD compared to CN participants. Within the AD group, CSF SV2A was highly correlated with SV2A PET. By contrast, other CSF proteins were generally higher in participants with AD and not associated with SV2A PET.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>We report a novel CSF assay for SV2A that is strongly correlated with the PET measurement of SV2A. Our results suggest that CSF SV2A may serve as a biomarker for synaptic density in AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Synaptic vesicle glycoprotein 2A (SV2A) measured by a novel cerebrospinal fluid (CSF) enzyme\u2010linked immunosorbent assay (ELISA) was lower in participants with symptomatic Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF SV2A was highly correlated with SV2A measured by positron emission tomography (PET) in participants with AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Other CSF synaptic\/axonal proteins were not significantly associated with SV2A PET.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF SV2A may serve as a biomarker for synaptic density in AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70344","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:11:14Z","timestamp":1749726674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Adam P.","family":"Mecca","sequence":"first","affiliation":[{"name":"Alzheimer's Disease Research Unit, Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of 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