{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:04:49Z","timestamp":1787025889880,"version":"build-2736575974"},"reference-count":51,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:p>Background: Synaptic disruption precedes neuronal death and correlates with clinical features of Alzheimer\u2019s disease (AD). The identification of fluid biomarkers of synaptic damage is emerging as a goal for early and accurate diagnosis of the disease. Objective: To perform a systematic review and meta-analysis to determine whether fluid biomarkers of synaptic damage are impaired in AD. Methods: PubMed, Scopus, EMBASE, and Web of Science were searched for articles reporting synaptic proteins as fluid biomarkers in AD and cognitively unimpaired (CU) individuals. Pooled effect sizes were determined using the Hedge G method with random effects. Questions adapted from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42021277487). Results: The search strategy identified 204 articles that were assessed for eligibility. A total of 23 studies were included in the systematic review and 15 were included in the meta-analysis. For Neurogranin, 827 AD and 1,237 CU subjects were included in the meta-analysis, showing a significant increase in cerebrospinal fluid of patients with AD compared to CU individuals, with an effect size of 1.01 (p\u200a&lt;\u200a0.001). A significant increase in SNAP-25 and GAP-43 levels in CSF of patients with AD was observed. Conclusion: Neurogranin, SNAP-25, and GAP-43 are possible biomarkers of synaptic damage in AD, and other potential synaptic biomarkers are emerging. This meta-analysis also revealed that there are still relatively few studies investigating these biomarkers in patients with AD or other dementias and showed wide heterogeneity in literature.<\/jats:p>","DOI":"10.3233\/jad-220515","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T11:44:17Z","timestamp":1666093457000},"page":"1381-1393","source":"Crossref","is-referenced-by-count":16,"title":["Synaptic Proteins as Fluid Biomarkers in Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.1177","volume":"90","author":[{"given":"Fausto","family":"Roveta","sequence":"first","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Cermelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Spina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rubino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Borsello","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences University of Milano, Milan, Italy"},{"name":"Mario Negri Institute for Pharmacological Research, University of Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vercelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, University of 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