Affiliations: [a] Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, Italy
| [b] Department of Pharmacological and Biomolecular Sciences University of Milano, Milan, Italy
| [c] Mario Negri Institute for Pharmacological Research, University of Milano, Milan, Italy
| [d] Neuroscience Institute Cavalieri Ottolenghi, University of Torino, Orbassano, Italy
Correspondence:
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Correspondence to: Fausto Roveta, MD, Department of Neuroscience Rita Levi Montalcini, University of Torino, via Cherasco 15 – 10126 Torino, Italy. Tel.: +39 0116334763; E-mail: fausto.roveta@unito.it.
Abstract: Background:Synaptic disruption precedes neuronal death and correlates with clinical features of Alzheimer’s 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 < 0.001). 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.
