{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:34:32Z","timestamp":1783953272625,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T00:00:00Z","timestamp":1610841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Strat-up Funding to OE from Qatar Biomedical Research Institute","award":["SF 2007\u2013007"],"award-info":[{"award-number":["SF 2007\u2013007"]}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRPNo.: 8\u2013517\u20133-112"],"award-info":[{"award-number":["NPRPNo.: 8\u2013517\u20133-112"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Total CSF \u03b1-synuclein (t-\u03b1-syn), phosphorylated \u03b1-syn (pS129-\u03b1-syn) and \u03b1-syn oligomers (o-\u03b1-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of \u03b1-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF \u03b1-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson\u2019s disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer\u2019s disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-\u03b1-syn\/\u03b1-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower \u03b1-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-\u03b1-syn levels (p = 0.002; cut-off value: \u2264865 pg\/mL; sensitivity: 95%, specificity: 69%) and higher pS129-\/t-\u03b1-syn ratios (p = 0.020; cut-off value: \u22650.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant \u03b1-syn species alterations in non-synucleinopathies.<\/jats:p>","DOI":"10.3390\/brainsci11010119","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T05:17:34Z","timestamp":1610947054000},"page":"119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cerebrospinal Fluid \u03b1-Synuclein Species in Cognitive and Movements Disorders"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-5009","authenticated-orcid":false,"given":"Vasilios C.","family":"Constantinides","sequence":"first","affiliation":[{"name":"Neurochemistry and Biomarkers Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"},{"name":"Ward of Cognitive and movement Disorders, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour K.","family":"Majbour","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Centre, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Paraskevas","sequence":"additional","affiliation":[{"name":"Neurochemistry and Biomarkers Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilham","family":"Abdi","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Centre, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bared","family":"Safieh-Garabedian","sequence":"additional","affiliation":[{"name":"College of Medicine, Member of QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Stefanis","sequence":"additional","affiliation":[{"name":"Ward of Cognitive and movement Disorders, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar M.","family":"El-Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Centre, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Kapaki","sequence":"additional","affiliation":[{"name":"Neurochemistry and Biomarkers Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"},{"name":"Ward of Cognitive and movement Disorders, 1st Department of Neurology, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1017\/S0317167100031814","article-title":"Accuracy of clinical diagnosis in parkinsonism\u2014A prospective study","volume":"18","author":"Rajput","year":"1991","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/mds.25327","article-title":"Accuracy of the National Institute for Neurological Disorders and Stroke\/Society for Progressive Supranuclear Palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy","volume":"28","author":"Respondek","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1001\/archneur.64.6.830","article-title":"Accuracy of the clinical evaluation for frontotemporal dementia","volume":"64","author":"Mendez","year":"2007","journal-title":"Arch Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/brain\/awf080","article-title":"The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service","volume":"125","author":"Hughes","year":"2002","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S1474-4422(11)70014-X","article-title":"alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: A cohort study","volume":"10","author":"Mollenhauer","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121ra20","DOI":"10.1126\/scitranslmed.3002566","article-title":"Phosphorylated alpha-synuclein in Parkinson\u2019s disease","volume":"4","author":"Wang","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/ana.22311","article-title":"Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression","volume":"69","author":"Shi","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1212\/WNL.0b013e3181fd613b","article-title":"Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease","volume":"75","author":"Tokuda","year":"2010","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1002\/mds.23670","article-title":"Cerebrospinal fluid Tau\/alpha-synuclein ratio in Parkinson\u2019s disease and degenerative dementias","volume":"26","author":"Parnetti","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"alpha-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00401-003-0811-1","article-title":"Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy","volume":"107","author":"Nishie","year":"2004","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1001\/archneur.65.12.1577","article-title":"Central role of alpha-synuclein oligomers in neurodegeneration in Parkinson disease","volume":"65","author":"Kazantsev","year":"2008","journal-title":"Arch Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1096\/fj.10-179192","article-title":"Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson\u2019s disease","volume":"25","author":"Foulds","year":"2011","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/alzrt255","article-title":"Levels of cerebrospinal fluid alpha-synuclein oligomers are increased in Parkinson\u2019s disease with dementia and dementia with Lewy bodies compared to Alzheimer\u2019s disease","volume":"6","author":"Hansson","year":"2014","journal-title":"Alzheimers Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/mds.111","article-title":"alpha-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies","volume":"33","author":"Majbour","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/mds.26754","article-title":"Longitudinal changes in CSF alpha-synuclein species reflect Parkinson\u2019s disease progression","volume":"31","author":"Majbour","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"40263","DOI":"10.1038\/srep40263","article-title":"Increased levels of CSF total but not oligomeric or phosphorylated forms of alpha-synuclein in patients diagnosed with probable Alzheimer\u2019s disease","volume":"7","author":"Majbour","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","article-title":"Second consensus statement on the diagnosis of multiple system atrophy","volume":"71","author":"Gilman","year":"2008","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria","volume":"32","author":"Hoglinger","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1212\/WNL.0b013e31827f0fd1","article-title":"Criteria for the diagnosis of corticobasal degeneration","volume":"80","author":"Armstrong","year":"2013","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(10)70299-4","article-title":"Behavioural-variant frontotemporal dementia: Diagnosis, clinical staging, and management","volume":"10","author":"Piguet","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/WAD.0000000000000034","article-title":"Diagnostic criteria for vascular cognitive disorders: A VASCOG statement","volume":"28","author":"Sachdev","year":"2014","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jalz.2016.09.008","article-title":"Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia","volume":"13","author":"Simonsen","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.jalz.2014.03.003","article-title":"The clinical use of cerebrospinal fluid biomarker testing for Alzheimer\u2019s disease diagnosis: A consensus paper from the Alzheimer\u2019s Biomarkers Standardization Initiative","volume":"10","author":"Molinuevo","year":"2014","journal-title":"Alzheimers Dement."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13024-016-0072-9","article-title":"Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson\u2019s disease","volume":"11","author":"Majbour","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2217\/bmm.12.46","article-title":"Recommendations to standardize preanalytical confounding factors in Alzheimer\u2019s and Parkinson\u2019s disease cerebrospinal fluid biomarkers: An update","volume":"6","author":"Mollenhauer","year":"2012","journal-title":"Biomark. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jns.2017.09.039","article-title":"CSF biomarkers beta-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes","volume":"382","author":"Constantinides","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000478979","article-title":"Cerebrospinal Fluid TAR DNA-Binding Protein 43 Combined with Tau Proteins as a Candidate Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Spectrum Disorders","volume":"44","author":"Bourbouli","year":"2017","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kapaki, E., Paraskevas, G.P., Emmanouilidou, E., and Vekrellis, K. (2013). The diagnostic value of CSF alpha-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081654"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3988\/jcn.2011.7.4.215","article-title":"Elevated levels of alpha-synuclein oligomer in the cerebrospinal fluid of drug-naive patients with Parkinson\u2019s disease","volume":"7","author":"Park","year":"2011","journal-title":"J. Clin. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1093\/brain\/awn349","article-title":"Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies","volume":"132","author":"Paleologou","year":"2009","journal-title":"Brain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1096\/fj.03-1449com","article-title":"Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson\u2019s disease","volume":"20","author":"Salem","year":"2006","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.biopsych.2014.12.019","article-title":"Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies","volume":"78","author":"Sengupta","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13195-014-0077-y","article-title":"Evaluating the relationship between amyloid-beta and alpha-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson\u2019s disease","volume":"6","author":"Swirski","year":"2014","journal-title":"Alzheimers Res. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000112832","article-title":"Red blood cells are the major source of alpha-synuclein in blood","volume":"5","author":"Barbour","year":"2008","journal-title":"Neurodegener. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/mds.27090","article-title":"A user\u2019s guide for alpha-synuclein biomarker studies in biological fluids: Perianalytical considerations","volume":"32","author":"Mollenhauer","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/jnc.14713","article-title":"Antibodies against alpha-synuclein: Tools and therapies","volume":"150","author":"Vaikath","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-015-0185-3","article-title":"Phosphorylated alpha-synuclein in Parkinson\u2019s disease: Correlation depends on disease severity","volume":"3","author":"Stewart","year":"2015","journal-title":"Acta Neuropathol Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fnagi.2014.00248","article-title":"Elevated levels of cerebrospinal fluid alpha-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers","volume":"6","author":"Aasly","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40035-020-00192-4","article-title":"CSF total and oligomeric alpha-Synuclein along with TNF-alpha as risk biomarkers for Parkinson\u2019s disease: A study in LRRK2 mutation carriers","volume":"9","author":"Majbour","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00415-014-7560-z","article-title":"Correlates of cerebrospinal fluid levels of oligomeric- and total-alpha-synuclein in premotor, motor and dementia stages of Parkinson\u2019s disease","volume":"262","author":"Compta","year":"2015","journal-title":"J. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0304-3940(98)00923-9","article-title":"A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy","volume":"259","author":"Urakami","year":"1999","journal-title":"Neurosci. Lett."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/1\/119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:12:13Z","timestamp":1760159533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/1\/119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,17]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["brainsci11010119"],"URL":"https:\/\/doi.org\/10.3390\/brainsci11010119","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,17]]}}}