{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:01:35Z","timestamp":1781701295347,"version":"3.54.5"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidade Federal Do Cear\u00e1"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sleep Breath"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Idiopathic REM sleep behavior disorder (iRBD) indicates an early \u03b1-synucleinopathy, offering a window for early detection and intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Explore a serum-based biomarker panel, comprising NfL, GFAP, t-tau, and UCH-L1, in patients with iRBD, and compare to individuals with synucleinopathy and healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This is a cross-sectional, observational study. Serum biomarkers were measured using the single molecule array technique. Clinical evaluation included standardized assessments of sleep, cognitive function, motor symptoms, and psychiatric features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GFAP levels were significantly higher in the iRBD group than in the control and synucleinopathy groups. Serum NfL levels yielded conflicting results. T-tau and UCHL-1 protein levels were lower in the iRBD and synucleinopathy groups compared to the control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that serum levels of NfL, GFAP, t-tau, and UCH-L1 may serve as potential biomarkers in iRBD, primarily GFAP levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11325-026-03698-9","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:54:57Z","timestamp":1778478897000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory serum biomarker profiling in idiopathic REM sleep behavior disorder: evidence of early neurodegenerative signatures: a pilot study"],"prefix":"10.1007","volume":"30","author":[{"given":"Danielle Mesquita","family":"Torres","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Henrique Queiroz","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marylane","family":"da Silva Viana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Michilles Santos","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Gabriela Barros","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Jos\u00e9 Rodrigues","family":"de Ara\u00fajo Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle Silva Tavares","family":"Sobreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca Charliane Almino","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annyta Fernandes","family":"Frota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Verde Ramos","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Titze-","family":"de- Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Braga-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle S.","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoel Alves","family":"Sobreira-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"1","key":"3698_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13024-025-00809-0","volume":"20","author":"A Stefani","year":"2025","unstructured":"Stefani A, Antelmi E, Arnaldi D, Arnulf I, During E, H\u00f6gl B et al (2025) From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease. Mol Neurodegener 20(1):19","journal-title":"Mol Neurodegener"},{"issue":"6","key":"3698_CR2","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1002\/mdc3.70006","volume":"12","author":"A Ophei","year":"2025","unstructured":"Ophei A, Rottgen S, Reichrath J, Kalibe E, Fink G, Sommerauner M (2025) Being prodromal: current criteria in the context of isolated REM sleep behavior disorder. Mov Disorders Clin Pract 12(6):828\u2013834","journal-title":"Mov Disorders Clin Pract"},{"issue":"3","key":"3698_CR3","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1093\/brain\/awz030","volume":"142","author":"RB Postuma","year":"2019","unstructured":"Postuma RB, Iranzo A, Hu M et al (2019) Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentric study. Brain 142(3):744\u2013759","journal-title":"Brain"},{"issue":"3","key":"3698_CR4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1177\/1535370217750088","volume":"243","author":"RM Califf","year":"2018","unstructured":"Califf RM (2018) Biomarker definitions and their applications. Exp Biol Med 243(3):213\u2013221","journal-title":"Exp Biol Med"},{"issue":"7","key":"3698_CR5","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1007\/s11064-023-03873-4","volume":"48","author":"VK Sharma","year":"2023","unstructured":"Sharma VK, Singh TG, Mehta V, Mannan A (2023) Biomarkers: role and scope in neurological disorders. Neurochem Res 48(7):2029\u20132058","journal-title":"Neurochem Res"},{"issue":"2","key":"3698_CR6","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/cts.12920","volume":"14","author":"J Kang","year":"2021","unstructured":"Kang J, Kim JW, Heo H, Lee J, Park KY, Yoon JH et al (2021) Identification of BAG2 and Cathepsin D as plasma biomarkers for Parkinson\u2019s disease. Clin Transl Sci 14(2):606\u2013616","journal-title":"Clin Transl Sci"},{"issue":"5","key":"3698_CR7","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/sj.cr.7290235","volume":"14","author":"V RACHAKONDA","year":"2004","unstructured":"Rachakonda V, Pan TH (2004) Biomarkers of neurodegenerative disorders: how good are they. Cell Res 14(5):349\u2013358","journal-title":"Cell Res"},{"issue":"1","key":"3698_CR8","doi-asserted-by":"publisher","first-page":"12136","DOI":"10.1038\/s41598-025-96926-3","volume":"15","author":"L Arnaldo","year":"2025","unstructured":"Arnaldo L, Mena J, Serradell M, Gaig C, Adamuz D, Vilas D, Samaniego D, Ispierto L, Montini A, May\u00e0 G, \u00c1lvarez R, Pastor P, Iranzo A, Beyer K (2025) Platelet miRNAs as early biomarkers for progression of idiopathic REM sleep behavior disorder to a synucleinopathy. Sci Rep 15(1):12136","journal-title":"Sci Rep"},{"issue":"9","key":"3698_CR9","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3390\/biomedicines9091272","volume":"9","author":"J Campdelacreu","year":"2021","unstructured":"Campdelacreu J, Vilas D, Ispierto L, Re\u00f1\u00e9 R, \u00c1lvarez R, Armengol M, P, Borr\u00e0s FE, Beyer, K (2021) Platelet miRNA biosignature discriminates between dementia with lewy bodies and Alzheimer\u2019s disease. Biomedicines 9(9):1272","journal-title":"Biomedicines"},{"issue":"1","key":"3698_CR10","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.1038\/s41598-023-32480-0","volume":"13","author":"P Youssef","year":"2023","unstructured":"Youssef P, Hughes L, Kim WS, Halliday GM, Lewis SJ, Coope A, Dzamko N (2023) Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson\u2019s disease biomarkers using multiplexed single molecule counting. Sci Rep 13(1):5217","journal-title":"Sci Rep"},{"issue":"12","key":"3698_CR11","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W et al (2015) MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov Disord 30(12):1591\u20131601","journal-title":"Mov Disord"},{"key":"3698_CR12","unstructured":"Troester M, Quan S, Berry R et al (2023) The AASM manual for the scoring of sleep and associated events: rules, terminology and clinicai specifications. 3rd ed. Darien I, (ed)"},{"key":"3698_CR13","unstructured":"American Academy of Sleep Medicine (2014) International classification of sleep disorders 3rd. Daril I (ed) lnternational classification of sleep disorders - third edition (ICSD-3). American Academy of Sleep Medicine"},{"issue":"6","key":"3698_CR14","doi-asserted-by":"publisher","first-page":"835","DOI":"10.5665\/sleep.1886","volume":"35","author":"B Frauscher","year":"2012","unstructured":"Frauscher B, Iranzo A, Gaig C et al (2012) SINBAR (Sleep Innsbruck Barcelona) Group. Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder. Sleep 35(6):835\u2013847","journal-title":"Sleep"},{"issue":"10","key":"3698_CR15","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","volume":"54","author":"J Kuhle","year":"2016","unstructured":"Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, Sandelius \u00c5 et al (2016) Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med (CCLM) 54(10):1655\u20131661","journal-title":"Clin Chem Lab Med (CCLM)"},{"issue":"3","key":"3698_CR16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S1474-4422(22)00009-6","volume":"21","author":"P Benkert","year":"2022","unstructured":"Benkert P, Meier S, Schaedelin S et al (2022) Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol 21(3):246\u2013257","journal-title":"Lancet Neurol"},{"issue":"4","key":"3698_CR17","doi-asserted-by":"publisher","first-page":"485","DOI":"10.3233\/JPD-223519","volume":"13","author":"X Zhang","year":"2023","unstructured":"Zhang X, Ma L, Liang D, Song B, Chen J, Huang Y et al (2023) Neurofilament light protein predicts disease progression in idiopathic REM sleep behavior disorder. J Parkinsons Dis 13(4):485\u2013499","journal-title":"J Parkinsons Dis"},{"issue":"2","key":"3698_CR18","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/jnc.15780","volume":"165","author":"X Teng","year":"2023","unstructured":"Teng X, Mao S, Wu H, Shao Q, Zu J, Zhang W et al (2023) The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the <\u2009scp>REM sleep behavior disorder subtype of Parkinson\u2019s disease. J Neurochem 165(2):268\u2013276","journal-title":"J Neurochem"},{"issue":"3","key":"3698_CR19","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1212\/WNL.57.3.560","volume":"57","author":"G De Savettieri","year":"2001","unstructured":"Savettieri G, De Marco EV, Civitelli D, Salemi G, Nicoletti G, Annesi G et al (2001) Lack of association between ubiquitin carboxy-terminal hydrolase L1 gene polymorphism and PD. Neurol 57(3):560\u2013561","journal-title":"Neurol"},{"issue":"2","key":"3698_CR20","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0304-3940(00)01510-X","volume":"293","author":"GD Mellick","year":"2000","unstructured":"Mellick GD, Silburn PA (2000) The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson\u2019s disease. Neurosci Lett 293(2):127\u2013130","journal-title":"Neurosci Lett"},{"issue":"9","key":"3698_CR21","doi-asserted-by":"publisher","first-page":"4836","DOI":"10.1007\/s00415-022-11120-z","volume":"269","author":"F Nabizadeh","year":"2022","unstructured":"Nabizadeh F, Pirahesh K, Valizadeh P (2022) REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson\u2019s disease: a cross-sectional and longitudinal study. J Neurol 269(9):4836\u20134845","journal-title":"J Neurol"},{"issue":"1","key":"3698_CR22","doi-asserted-by":"publisher","first-page":"14820","DOI":"10.1038\/s41598-021-94345-8","volume":"11","author":"MS Baek","year":"2021","unstructured":"Baek MS, Lee MJ, Kim HK, Lyoo CH (2021) Temporal trajectory of biofluid markers in Parkinson\u2019s disease. Sci Rep 11(1):14820","journal-title":"Sci Rep"}],"container-title":["Sleep and Breathing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11325-026-03698-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11325-026-03698-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11325-026-03698-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:26:42Z","timestamp":1781699202000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11325-026-03698-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["3698"],"URL":"https:\/\/doi.org\/10.1007\/s11325-026-03698-9","relation":{},"ISSN":["1520-9512","1522-1709"],"issn-type":[{"value":"1520-9512","type":"print"},{"value":"1522-1709","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"3 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee (Ethics Committee of HU-UFC) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of HU-UFC, under the protocol number (CAAE 74817423.8.10015045). Informed consent was obtained from all individualparticipants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers\u2019 bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"AI resources were used solely for language improvement.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement regarding the use of AI"}},{"value":"This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq). All authors deny other sources of funding and conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Financial disclosures of all authors (for the preceding 12 months)"}}],"article-number":"158"}}