{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:49:23Z","timestamp":1790192963325,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Biomarkers are increasingly recognized as tools in the diagnosis and prognosis of neurodegenerative diseases. No fluid biomarker for Parkinson\u2019s disease (PD) has been established to date, but \u03b1-synuclein, a major component of Lewy bodies in PD and dementia with Lewy bodies (DLB), has become a promising candidate. Here, we investigated CSF \u03b1-synuclein in patients with PD (n = 28), PDD (n = 8), and DLB (n = 5), applying an electrochemiluminescence immunoassay. Median values were non-significantly (p = 0.430) higher in patients with PDD and DLB (287 pg\/mL) than in PD (236 pg\/mL). A group of n = 36 primarily non-demented patients with PD and PDD was clinically followed for up to two years. A higher baseline \u03b1-synuclein was associated with increases in Hoehn and Yahr classifications (p = 0.019) and Beck Depression Inventory scores (p &lt; 0.001) as well as worse performance in Trail Making Test A (p = 0.017), Trail Making Test B (p = 0.043), and the Boston Naming Test (p = 0.002) at follow-up. Surprisingly, higher levels were associated with a better performance in semantic verbal fluency tests (p = 0.046). In summary, CSF \u03b1-synuclein may be a potential prognostic marker for disease progression, affective symptoms, and executive cognitive function in PD. Larger-scaled studies have to validate these findings and the discordant results for single cognitive tests in this exploratory investigation.<\/jats:p>","DOI":"10.3390\/diagnostics12051259","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:59:37Z","timestamp":1652875177000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Baseline Cerebrospinal Fluid \u03b1-Synuclein in Parkinson\u2019s Disease Is Associated with Disease Progression and Cognitive Decline"],"prefix":"10.3390","volume":"12","author":[{"given":"Anna","family":"Emdina","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Varges","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Nuhn","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Goebel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Bunck","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Maass","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5502-681X","authenticated-orcid":false,"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-7497","authenticated-orcid":false,"given":"Franc","family":"Llorens","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Kruse","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Medical Centre G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7096","authenticated-orcid":false,"given":"Paul","family":"Lingor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Paracelsus-Elena-Klinik, 34128 Kassel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-2463","authenticated-orcid":false,"given":"Inga","family":"Zerr","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_2","unstructured":"GBD 2016 Parkinson\u2019s Disease Collaborators (2018). Global, regional, and national burden of Parkinson\u2019s disease, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 939\u2013953."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrneurol.2012.242","article-title":"100 years of Lewy pathology","volume":"9","author":"Goedert","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/jnc.14965","article-title":"Synucleinopathies: Where we are and where we need to go","volume":"153","author":"Gerhardt","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrn3406","article-title":"The many faces of \u03b1-synuclein: From structure and toxicity to therapeutic target","volume":"14","author":"Lashuel","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/mds.25373","article-title":"Parkinson\u2019s disease and alpha synuclein: Is Parkinson\u2019s disease a prion-like disorder?","volume":"28","author":"Olanow","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E4949","DOI":"10.1073\/pnas.1513426112","article-title":"Propagation of prions causing synucleinopathies in cultured cells","volume":"112","author":"Woerman","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1212\/WNL.56.6.730","article-title":"Risk of dementia in Parkinson\u2019s disease: A community-based, prospective study","volume":"56","author":"Aarsland","year":"2001","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","article-title":"Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium","volume":"89","author":"McKeith","year":"2017","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jellinger, K.A., and Korczyn, A.D. (2018). Are dementia with Lewy bodies and Parkinson\u2019s disease dementia the same disease?. BMC Med., 16.","DOI":"10.1186\/s12916-018-1016-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1468-1331.2008.02513.x","article-title":"Reisensburg Working Group for Tauopathies with Parkinsonism. Tauopathies with parkinsonism: Clinical spectrum, neuropathologic basis, biological markers, and treatment options","volume":"16","author":"Ludolph","year":"2009","journal-title":"Eur. J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"887","DOI":"10.4103\/0028-3886.91371","article-title":"Dual pathology of corticobasal degeneration and Parkinson\u2019s disease in a patient with clinical features of progressive supranuclear palsy","volume":"59","author":"Mooney","year":"2011","journal-title":"Neurol. India"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fneur.2020.00180","article-title":"Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P)\u2014A Clinical Challenge at the Boundaries of PSP and Parkinson\u2019s Disease (PD)","volume":"11","author":"Alster","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"572976","DOI":"10.3389\/fneur.2020.572976","article-title":"Neuroimaging Advances in Parkinson\u2019s Disease and Atypical Parkinsonian Syndromes","volume":"11","author":"Saeed","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S1474-4422(11)70014-X","article-title":"\u03b1-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_16","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_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1026\/\/0012-1924.46.1.38","article-title":"Vorschlag zur Vereinfachung des Beck-Depressions-Inventars (BDI)","volume":"46","author":"Schmitt","year":"2000","journal-title":"Diagnostica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000357774","article-title":"The Extension of the German CERAD Neuropsychological Assessment Battery with Tests Assessing Subcortical, Executive and Frontal Functions Improves Accuracy in Dementia Diagnosis","volume":"4","author":"Schmid","year":"2014","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"ref_19","unstructured":"Fahn, S., Marsden, C.D., Goldstein, M., Stoker, T.B., and Barker, R.A. (1987). Unified Parkinson\u2019s disease rating scale IN. Recent Developments in Parkinson\u2019s Disease, Macmillan Healthcare Information."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/mds.20213","article-title":"Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations","volume":"19","author":"Goetz","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1007\/s00415-015-7837-x","article-title":"Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of A.D and sCJD","volume":"262","author":"Llorens","year":"2015","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1007\/s12035-017-0479-5","article-title":"Validation of \u03b1-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease","volume":"55","author":"Llorens","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s00391-009-0031-y","article-title":"CERAD-NP-Testbatterie: Alters-, geschlechts- und bildungsspezifische Normen ausgew\u00e4hlter Subtests. Ergebnisse der German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe) [CERAD-NP battery: Age-, gender- and education-specific reference values for selected subtests. Results of the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe)]","volume":"42","author":"Luck","year":"2009","journal-title":"Z. Gerontol. Geriatr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Verbeke, G., and Molenberghs, G. (2000). Linear Mixed Models for Longitudinal Data, Springer.","DOI":"10.1007\/978-1-4419-0300-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Soft."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/jnc.14809","article-title":"Parkinson\u2019s disease biomarkers based on \u03b1-synuclein","volume":"150","author":"Fayyad","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3109\/00207454.2014.961454","article-title":"Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson\u2019s disease diagnosis: A systematic review and meta-analysis","volume":"125","author":"Gao","year":"2015","journal-title":"Int. J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2217\/BMM.14.105","article-title":"The utility of \u03b1-synuclein as biofluid marker in neurodegenerative diseases: A systematic review of the literature","volume":"10","author":"Simonsen","year":"2016","journal-title":"Biomark. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s00415-016-8259-0","article-title":"Cerebrospinal \u03b1-synuclein in \u03b1-synuclein aggregation disorders: Tau\/\u03b1-synuclein ratio as potential biomarker for dementia with Lewy bodies","volume":"263","author":"Llorens","year":"2016","journal-title":"J. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/mds.27806","article-title":"Longitudinal analyses of cerebrospinal fluid \u03b1-Synuclein in prodromal and early Parkinson\u2019s disease","volume":"34","author":"Mollenhauer","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1001\/archneurol.2012.1654","article-title":"Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and\/or parkinsonian disorders","volume":"69","author":"Hall","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/ene.12176","article-title":"Reduced \u03b1-synuclein levels in cerebrospinal fluid in Parkinson\u2019s disease are unrelated to clinical and imaging measures of disease severity","volume":"21","author":"Bidinosti","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/mds.26578","article-title":"Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson\u2019s Disease","volume":"31","author":"Hall","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1212\/WNL.0000000000001098","article-title":"CSF biomarkers and clinical progression of Parkinson disease","volume":"84","author":"Hall","year":"2015","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.parkreldis.2021.07.034","article-title":"A new CERAD total score with equally weighted z-scores and additional executive and non-amnestic \u201cCERAD-Plus\u201d tests enhances cognitive diagnosis in patients with Parkinson\u2019s disease: Evidence from the LANDSCAPE study","volume":"90","author":"Lillig","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_36","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-\u03b1-synuclein in premotor, motor and dementia stages of Parkinson\u2019s disease","volume":"262","author":"Compta","year":"2015","journal-title":"J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.parkreldis.2015.04.027","article-title":"Amyloid-\u03b2 and \u03b1-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson\u2019s disease","volume":"21","author":"Stav","year":"2015","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/mds.22875","article-title":"Progression of Parkinson\u2019s disease as evaluated by Hoehn and Yahr stage transition times","volume":"25","author":"Zhao","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1750-3639.2009.00369.x","article-title":"The epidemiology of dementia associated with Parkinson\u2019s disease","volume":"20","author":"Aarsland","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1212\/WNL.0000000000002651","article-title":"Monitoring of 30 marker candidates in early Parkinson disease as progression markers","volume":"87","author":"Mollenhauer","year":"2016","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1192\/bjp.180.2.148","article-title":"Subcortical dementia","volume":"180","author":"Turner","year":"2002","journal-title":"Br. J. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1037\/neu0000795","article-title":"Dynamic interplay of cognitive functioning and depressive symptoms in patients with Parkinson\u2019s disease","volume":"36","author":"Schroeders","year":"2022","journal-title":"Neuropsychology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/WAD.0b013e3181b76415","article-title":"The CERAD Neuropsychologic Battery Total Score and the Progression of Alzheimer Disease","volume":"24","author":"Rossetti","year":"2010","journal-title":"Alzheimer. Dis. Assoc. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ejma, M., Madetko, N., Brzecka, A., Guranski, K., Alster, P., Misiuk-Hoj\u0142o, M., Somasundaram, S.G., Kirkland, C.E., and Aliev, G. (2020). The Links between Parkinson\u2019s Disease and Cancer. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100416"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1007\/s12035-018-1313-4","article-title":"Cerebrospinal Fluid Total and Phosphorylated \u03b1-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy","volume":"56","author":"Schmitz","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"717930","DOI":"10.3389\/fnagi.2021.717930","article-title":"Detection of Cerebrospinal Fluid Neurofilament Light Chain as a Marker for Alpha-Synucleinopathies","volume":"13","author":"Canaslan","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/mds.28206","article-title":"Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson\u2019s Disease Progression","volume":"35","author":"Mollenhauer","year":"2020","journal-title":"Mov. Disord."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:14:21Z","timestamp":1760138061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,18]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051259"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051259","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,18]]}}}