{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:17:29Z","timestamp":1757312249155,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Postoperative delirium (POD) is a common postoperative complication, which may be associated with \u03b1-synuclein (\u03b1-syn). The purpose of this study was to explore the association between the expression level of \u03b1-syn in cerebrospinal fluid (CSF) and POD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a prospective observational cohort study, which involved in 740 participants (mean age of 61.86 years, range 40\u201390 years; 40% female) from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. POD was diagnosed using the Confusion Assessment Scale (CAM), and its severity was measured using the Memorial Delirium Assessment Scale (MDAS). Enzyme-linked immune-sorbent assay (ELISA) was used to detect the concentrations of \u03b1-syn, A\u03b240, A\u03b242, T-tau, and P-tau in CSF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The incidence of POD was 11.22% (83\/740). The logistic regression analysis showed that the increased concentrations of CSF \u03b1-syn (OR = 1.005, 95%CI 1.004\u20131.006, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), P-tau (OR = 1.093, 95%CI 1.071\u20131.115, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), and T-tau (OR = 1.008, 95%CI 1.006\u20131.009, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) were risk factors of POD. Linear regression showed that CSF \u03b1-syn had positive correlations with P-tau (\u03b2 = 0.480, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), T-tau (\u03b2 = 0.334, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), while negative correlations with A\u03b240 (\u03b2 = \u20130.378 <jats:italic>P<\/jats:italic> &amp;lt; 0.001), A\u03b242 (\u03b2 = -0.800, <jats:italic>P<\/jats:italic> = 0.001) in POD patients. Mediation analyses showed the association between \u03b1-syn and POD was partially mediated by tau pathologies (proportion: 16\u201317%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CSF \u03b1-syn is one of the preoperative risk factors for POD, which may be mediated through tau pathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>[<jats:ext-link>www.ClinicalTrials.gov<\/jats:ext-link>], identifier [ChiCTR20 00033439].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.935869","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T05:17:36Z","timestamp":1666588656000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential value of cerebrospinal fluid \u03b1-synuclein in the identification of postoperative delirium undergoing knee\/hip arthroplasty: The perioperative neurocognitive disorder and biomarker lifestyle study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xu","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlin","family":"Bi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-315821","article-title":"Novel evidence associates higher plasma \u03b1-synuclein levels and cognitive impairment in Parkinson\u2019s disease.","volume":"88","author":"Aarsland","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0006-8993(00)03082-1","article-title":"Alpha-synuclein-positive structures in cases with sporadic Alzheimer\u2019s disease: Morphology and its relationship to tau aggregation.","volume":"888","author":"Arai","year":"2001","journal-title":"Brain Res."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026609","article-title":"Tau enhances \u03b1-synuclein aggregation and toxicity in cellular models of synucleinopathy.","volume":"6","author":"Badiola","year":"2011","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.bja.2020.08.061","article-title":"Association between plasma tau and postoperative delirium incidence and severity: A prospective observational study.","volume":"126","author":"Ballweg","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"B5","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S1474-4422(11)70072-2","article-title":"The projected effect of risk factor reduction on Alzheimer\u2019s disease prevalence.","volume":"10","author":"Barnes","year":"2011","journal-title":"Lancet Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.jalz.2015.05.016","article-title":"Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.","volume":"11","author":"Baumgart","year":"2015","journal-title":"Alzheimers Dement."},{"key":"B7","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3233\/JPD-150642","article-title":"The Synaptic Function of \u03b1-Synuclein.","volume":"5","author":"Burr\u00e9","year":"2015","journal-title":"J. Parkinsons Dis."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.823","article-title":"Impact of Race\/Ethnicity on Pain Management Outcomes in a Community-Based Teaching Hospital Following Inpatient Palliative Care Consultation.","volume":"8","author":"Chung","year":"2016","journal-title":"Cureus"},{"key":"B9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/NEN.0b013e3181927577","article-title":"Early-onset familial lewy body dementia with extensive tauopathy: A clinical, genetic, and neuropathological study.","volume":"68","author":"Clarim\u00f3n","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7281","DOI":"10.1523\/JNEUROSCI.0490-10.2010","article-title":"Synergistic Interactions between Abeta, tau, and alpha-synuclein: Acceleration of neuropathology and cognitive decline.","volume":"30","author":"Clinton","year":"2010","journal-title":"J. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families.","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1097\/SLA.0000000000002684","article-title":"CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study.","volume":"269","author":"Cunningham","year":"2019","journal-title":"Ann. Surg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"9220","DOI":"10.1523\/JNEUROSCI.2617-07.2007","article-title":"Different species of alpha-synuclein oligomers induce calcium influx and seeding.","volume":"27","author":"Danzer","year":"2007","journal-title":"J. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00560","article-title":"Longitudinal Alterations of Alpha-Synuclein, Amyloid Beta, Total, and Phosphorylated Tau in Cerebrospinal Fluid and Correlations Between Their Changes in Parkinson\u2019s Disease.","volume":"9","author":"Dolatshahi","year":"2018","journal-title":"Front. Neurol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25030600","article-title":"Alternative Structures of \u03b1-Synuclein.","volume":"5","author":"Du\u0142ak","year":"2020","journal-title":"Molecules"},{"key":"B16","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S1474-4422(17)30159-X","article-title":"Strategic roadmap for an early diagnosis of Alzheimer\u2019s disease based on biomarkers.","volume":"16","author":"Frisoni","year":"2017","journal-title":"Lancet Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1002\/ana.20819","article-title":"Interface between tauopathies and synucleinopathies: A tale of two proteins.","volume":"59","author":"Galpern","year":"2006","journal-title":"Ann. Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1126\/science.1082324","article-title":"Initiation and synergistic fibrillization of tau and alpha-synuclein.","volume":"300","author":"Giasson","year":"2003","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s11010-008-0008-y","article-title":"The role of alpha-synuclein in brain lipid metabolism: A downstream impact on brain inflammatory response.","volume":"326","author":"Golovko","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1523\/JNEUROSCI.2507-13.2014","article-title":"\u03b1-Synuclein is localized to mitochondria-associated ER membranes.","volume":"34","author":"Guardia-Laguarta","year":"2014","journal-title":"J. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1093\/brain\/awaa090","article-title":"Microglial exosomes facilitate \u03b1-synuclein transmission in Parkinson\u2019s disease.","volume":"143","author":"Guo","year":"2020","journal-title":"Brain"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010-2050) estimated using the 2010 census.","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.jalz.2016.09.009","article-title":"Recommendations for cerebrospinal fluid Alzheimer\u2019s disease biomarkers in the diagnostic evaluation of mild cognitive impairment.","volume":"13","author":"Herukka","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B24","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","article-title":"Delirium in elderly people.","volume":"383","author":"Inouye","year":"2014","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.bja.2020.06.063","article-title":"Postoperative delirium: Perioperative assessment, risk reduction, and management.","volume":"125","author":"Jin","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195749","article-title":"Parkinson\u2019s disease-related non-motor features as risk factors for post-operative delirium in spinal surgery.","volume":"13","author":"Kim","year":"2018","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease.","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"10253","DOI":"10.1523\/JNEUROSCI.0581-12.2012","article-title":"Soluble \u03b1-synuclein is a novel modulator of Alzheimer\u2019s disease pathophysiology.","volume":"32","author":"Larson","year":"2012","journal-title":"J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.tins.2004.01.007","article-title":"More than just two peas in a pod: Common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases.","volume":"27","author":"Lee","year":"2004","journal-title":"Trends Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy.","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/s11064-006-9140-9","article-title":"Interaction between Abeta peptide and alpha synuclein: Molecular mechanisms in overlapping pathology of Alzheimer\u2019s and Parkinson\u2019s in dementia with Lewy body disease.","volume":"31","author":"Mandal","year":"2006","journal-title":"Neurochem. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.neuron.2009.12.023","article-title":"Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis.","volume":"65","author":"Nemani","year":"2010","journal-title":"Neuron"},{"key":"B34","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","article-title":"CSF and blood biomarkers for the diagnosis of Alzheimer\u2019s disease: A systematic review and meta-analysis.","volume":"15","author":"Olsson","year":"2016","journal-title":"Lancet Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1007\/s11064-013-0982-7","article-title":"Effect of \u03b1-synuclein on amyloid \u03b2-induced toxicity: Relevance to Lewy body variant of Alzheimer disease.","volume":"38","author":"Resende","year":"2013","journal-title":"Neurochem. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1093\/hmg\/ddu011","article-title":"Interactions between Tau and \u03b1-synuclein augment neurotoxicity in a Drosophila model of Parkinson\u2019s disease.","volume":"23","author":"Roy","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1213\/ANE.0b013e3182147f6d","article-title":"Review articles: Postoperative delirium: Acute change with long-term implications.","volume":"112","author":"Rudolph","year":"2011","journal-title":"Anesth. Analg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"8083","DOI":"10.1523\/JNEUROSCI.1091-10.2010","article-title":"A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration.","volume":"30","author":"Scott","year":"2010","journal-title":"J. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00297","article-title":"Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery.","volume":"6","author":"Shi","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.febslet.2004.03.063","article-title":"Alpha-Synuclein regulation of the dopaminergic transporter: A possible role in the pathogenesis of Parkinson\u2019s disease.","volume":"565","author":"Sidhu","year":"2004","journal-title":"FEBS Lett."},{"key":"B41","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.anclin.2010.11.011","article-title":"Preventing postoperative complications in the elderly.","volume":"29","author":"Sieber","year":"2011","journal-title":"Anesthesiol. Clin."},{"key":"B42","doi-asserted-by":"publisher","first-page":"S290","DOI":"10.1016\/j.jalz.2013.10.004","article-title":"Increased CSF \u03b1-synuclein levels in Alzheimer\u2019s disease: Correlation with tau levels.","volume":"10","author":"Slaets","year":"2014","journal-title":"Alzheimers Dement."},{"key":"B43","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/jnc.14810","article-title":"The physiological role of \u03b1-synuclein and its relationship to Parkinson\u2019s Disease.","volume":"150","author":"Sulzer","year":"2019","journal-title":"J. Neurochem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00401-013-1148-z","article-title":"\u03b1-synuclein improves diagnostic and prognostic performance of CSF tau and A\u03b2 in Alzheimer\u2019s disease.","volume":"126","author":"Toledo","year":"2013","journal-title":"Acta Neuropathol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/acn3.58","article-title":"Preoperative cerebrospinal fluid \u03b2-Amyloid\/Tau ratio and postoperative delirium.","volume":"1","author":"Xie","year":"2014","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s40520-016-0541-6","article-title":"Risk factors for postoperative delirium following hip fracture repair in elderly patients: A systematic review and meta-analysis.","volume":"29","author":"Yang","year":"2017","journal-title":"Aging Clin. Exp. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1001\/jama.2016.181","article-title":"Delirium: An Important Postoperative Complication.","volume":"317","author":"Zenilman","year":"2017","journal-title":"JAMA"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.935869\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T05:17:39Z","timestamp":1666588659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.935869\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,24]]},"references-count":47,"alternative-id":["10.3389\/fnins.2022.935869"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.935869","relation":{},"ISSN":["1662-453X"],"issn-type":[{"type":"electronic","value":"1662-453X"}],"subject":[],"published":{"date-parts":[[2022,10,24]]},"article-number":"935869"}}