{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:59:39Z","timestamp":1782755979568,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["PD\u2010Strat project (FKZ 031L0137B)"],"award-info":[{"award-number":["PD\u2010Strat project (FKZ 031L0137B)"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["PDdementia"],"award-info":[{"award-number":["PDdementia"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen","doi-asserted-by":"publisher","award":["PD research; MIGAP study"],"award-info":[{"award-number":["PD research; MIGAP study"]}],"id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Molecular pathways associated with \u03b1\u2010synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin\u2010proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to evaluate CSF protein profiles of pathways related to \u03b1\u2010synuclein proteostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with \u03b1\u2010synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated \u03b1\u2010synuclein pathology with pronounced clinical trajectories.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by <jats:italic>GBA<\/jats:italic> variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total \u03b1\u2010synuclein, with lower levels of proteostasis proteins related to lower levels of total \u03b1\u2010synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of \u03b1\u2010synuclein longitudinally compared with PD patients with a normal proteostasis profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to \u03b1\u2010synuclein proteostasis in PD and DLB. \u00a9 2021 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28704","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T06:38:30Z","timestamp":1624862310000},"page":"2595-2604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<scp>CSF<\/scp> Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in <scp>PD<\/scp> and <scp>DLB<\/scp>"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-004X","authenticated-orcid":false,"given":"Stefanie","family":"Lerche","sequence":"first","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Sj\u00f6din","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Brinkmalm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Wurster","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Roeben","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Kathrin","family":"Hauser","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Liepelt\u2010Scarfone","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Waniek","sequence":"additional","affiliation":[{"name":"Roboscreen GmbH  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingolf","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Roboscreen GmbH  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gasser","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London United Kingdom"},{"name":"UK Dementia Research Institute at UCL  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-8596","authenticated-orcid":false,"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[{"name":"Center of Neurology, Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322338"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0533-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59414-4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10459"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000187889.17253.b1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20213"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c34b47"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.14779"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15327752jpa6703_13"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201700131"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0027"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021405"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-013-1020-2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91940-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(03)00037-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00388-2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194674"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-015-0166-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00265"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0309-3"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322493"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b28601"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.1925"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx285"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12247"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27806"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27884"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27731"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt367"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5028"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23614"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1090-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687787"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208046200"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27867"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28704","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.28704","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28704","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:12:00Z","timestamp":1760958720000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.28704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/mds.28704"],"URL":"https:\/\/doi.org\/10.1002\/mds.28704","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,28]]},"assertion":[{"value":"2021-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}