{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:43:19Z","timestamp":1794012199779,"version":"4.8.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson\u2019s disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years. Mixed-effects regression analyzed changes in NFL and the association with annual changes in MMSE and UPDRS-III scores over 10 years. PD patients had elevated serum NFL at all visits and a faster annual increase over 5 years compared to controls (0.09\u2009pg\/mL per year;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.029). Higher baseline NFL predicted faster cognitive decline \u03b2 \u22120.77 transformed MMSE;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.010), and a 40% NFL increase predicted future motor decline (\u03b2 0.28 UPDRS-III;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004). Elevated serum NFL in early PD is linked to faster cognitive and motor impairment, suggesting its prognostic value in PD biomarker panels.\n                  <\/jats:p>","DOI":"10.1038\/s41531-024-00768-1","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T08:09:27Z","timestamp":1724314167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson\u2019s Disease"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6521-741X","authenticated-orcid":false,"given":"Camilla Christina","family":"Pedersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9481-0932","authenticated-orcid":false,"given":"Anastasia","family":"Ushakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-2870","authenticated-orcid":false,"given":"Guido","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole-Bj\u00f8rn","family":"Tysnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-0078","authenticated-orcid":false,"given":"Jodi","family":"Maple-Gr\u00f8dem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0604-4891","authenticated-orcid":false,"given":"Johannes","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"768_CR1","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","volume":"90","author":"L Gaetani","year":"2019","unstructured":"Gaetani, L. et al. Neurofilament light chain as a biomarker in neurological disorders. J. Neurol. Neurosurg. Psychiatry 90, 870\u2013881 (2019).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"768_CR2","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","volume":"76","author":"C Bridel","year":"2019","unstructured":"Bridel, C. et al. Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. JAMA Neurol. 76, 1035\u20131048 (2019).","journal-title":"JAMA Neurol."},{"key":"768_CR3","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","volume":"14","author":"M Khalil","year":"2018","unstructured":"Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577\u2013589 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"768_CR4","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/s41531-022-00384-x","volume":"8","author":"L Batzu","year":"2022","unstructured":"Batzu, L. et al. Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson\u2019s disease. NPJ Parkinsons Dis. 8, 154 (2022).","journal-title":"NPJ Parkinsons Dis."},{"key":"768_CR5","doi-asserted-by":"publisher","first-page":"2945","DOI":"10.1002\/mds.28779","volume":"36","author":"WW Aamodt","year":"2021","unstructured":"Aamodt, W. W. et al. Neurofilament light chain as a biomarker for cognitive decline in Parkinson disease. Mov. Disord. 36, 2945\u20132950 (2021).","journal-title":"Mov. Disord."},{"key":"768_CR6","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.3233\/JPD-212535","volume":"11","author":"L-Z Ma","year":"2021","unstructured":"Ma, L.-Z. et al. Serum neurofilament dynamics predicts cognitive progression in de novo Parkinson\u2019s disease. J. Parkinsons Dis. 11, 1117\u20131127 (2021).","journal-title":"J. Parkinsons Dis."},{"key":"768_CR7","doi-asserted-by":"crossref","unstructured":"Liu, Y., Dou, K., Xue, L., Li, X. & Xie, A. Neurofilament light as a biomarker for motor decline in Parkinson\u2019s disease. Front. Neurosci. 16, 959261 (2022).","DOI":"10.3389\/fnins.2022.959261"},{"key":"768_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.parkreldis.2021.04.016","volume":"87","author":"A Pilotto","year":"2021","unstructured":"Pilotto, A. et al. Plasma NfL, clinical subtypes and motor progression in Parkinson\u2019s disease. Parkinsonism Relat. Disord. 87, 41\u201347 (2021).","journal-title":"Parkinsonism Relat. Disord."},{"key":"768_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.805953","volume":"16","author":"Q Li","year":"2022","unstructured":"Li, Q. et al. A panel of plasma biomarkers for differential diagnosis of Parkinsonian syndromes. Front. Neurosci. 16, 805953 (2022).","journal-title":"Front. Neurosci."},{"key":"768_CR10","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.parkreldis.2021.07.028","volume":"90","author":"L Niemann","year":"2021","unstructured":"Niemann, L. et al. Serum neurofilament is associated with motor function, cognitive decline and subclinical cardiac damage in advanced Parkinson\u2019s disease (MARK-PD). Parkinsonism Relat. Disord. 90, 44\u201348 (2021).","journal-title":"Parkinsonism Relat. Disord."},{"key":"768_CR11","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13024-020-00385-5","volume":"15","author":"ASL Ng","year":"2020","unstructured":"Ng, A. S. L. et al. Utility of plasma neurofilament light as a diagnostic and prognostic biomarker of the postural instability gait disorder motor subtype in early Parkinson\u2019s disease. Mol. Neurodegener. 15, 33 (2020).","journal-title":"Mol. Neurodegener."},{"key":"768_CR12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jocn.2023.01.015","volume":"110","author":"F Nabizadeh","year":"2023","unstructured":"Nabizadeh, F., Mohamadzadeh, O., Hosseini, H., Rasouli, K. & Afyouni, N. E. Serum neurofilament light chain in LRRK2 related Parkinson\u2019s disease: a five years follow-up. J. Clin. Neurosci. 110, 12\u201318 (2023).","journal-title":"J. Clin. Neurosci."},{"key":"768_CR13","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/jnc.15780","volume":"165","author":"X Teng","year":"2023","unstructured":"Teng, X. et al. The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson\u2019s disease. J. Neurochem. 165, 268\u2013276 (2023).","journal-title":"J. Neurochem."},{"key":"768_CR14","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1002\/mds.28738","volume":"36","author":"I Schulz","year":"2021","unstructured":"Schulz, I. et al. Systematic assessment of 10 biomarker candidates focusing on \u03b1-synuclein-related disorders. Mov. Disord. 36, 2874\u20132887 (2021).","journal-title":"Mov. Disord."},{"key":"768_CR15","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41531-021-00232-4","volume":"7","author":"C Quadalti","year":"2021","unstructured":"Quadalti, C. et al. Neurofilament light chain and \u03b1-synuclein RT-QuIC as differential diagnostic biomarkers in parkinsonisms and related syndromes. NPJ Parkinsons Dis. 7, 93 (2021).","journal-title":"NPJ Parkinsons Dis."},{"key":"768_CR16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/mds.27897","volume":"35","author":"LP Oosterveld","year":"2020","unstructured":"Oosterveld, L. P. et al. CSF or serum neurofilament light added to \u03b1-Synuclein panel discriminates Parkinson\u2019s from controls. Mov. Disord. 35, 288\u2013295 (2020).","journal-title":"Mov. Disord."},{"key":"768_CR17","doi-asserted-by":"crossref","unstructured":"Buhmann, C., Magnus, T. & Choe, C.-U. Blood neurofilament light chain in Parkinson\u2019s disease. J. Neural Transm. 130, 755\u2013762 (2023).","DOI":"10.1007\/s00702-023-02632-7"},{"key":"768_CR18","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1136\/jnnp-2021-328365","volume":"93","author":"N Vijiaratnam","year":"2022","unstructured":"Vijiaratnam, N. et al. Combining biomarkers for prognostic modelling of Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 93, 707\u2013715 (2022).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"768_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01228-7","volume":"21","author":"JA Watt","year":"2021","unstructured":"Watt, J. A., Veroniki, A. A., Tricco, A. C. & Straus, S. E. Using a distribution-based approach and systematic review methods to derive minimum clinically important differences. BMC Med. Res. Methodol. 21, 41 (2021).","journal-title":"BMC Med. Res. Methodol."},{"key":"768_CR20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.parkreldis.2021.02.008","volume":"85","author":"R Ye","year":"2021","unstructured":"Ye, R. et al. Serum NFL levels predict progression of motor impairment and reduction in putamen dopamine transporter binding ratios in de novo Parkinson\u2019s disease: an 8-year longitudinal study. Parkinsonism Relat. Disord. 85, 11\u201316 (2021).","journal-title":"Parkinsonism Relat. Disord."},{"key":"768_CR21","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/mds.25070","volume":"27","author":"S Lessig","year":"2012","unstructured":"Lessig, S., Nie, D., Xu, R. & Corey-Bloom, J. Changes on brief cognitive instruments over time in Parkinson\u2019s disease. Mov. Disord. 27, 1125\u20131128 (2012).","journal-title":"Mov. Disord."},{"key":"768_CR22","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.parkreldis.2018.05.027","volume":"55","author":"AD Macleod","year":"2018","unstructured":"Macleod, A. D. et al. Age-related selection bias in Parkinson\u2019s disease research: are we recruiting the right participants? Parkinsonism Relat. Disord. 55, 128\u2013133 (2018).","journal-title":"Parkinsonism Relat. Disord."},{"key":"768_CR23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41531-024-00667-5","volume":"10","author":"BK Beaulieu-Jones","year":"2024","unstructured":"Beaulieu-Jones, B. K. et al. Disease progression strikingly differs in research and real-world Parkinson\u2019s populations. NPJ Parkinsons Dis. 10, 58 (2024).","journal-title":"NPJ Parkinsons Dis."},{"key":"768_CR24","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1136\/jnnp.2008.168211","volume":"80","author":"G Alves","year":"2009","unstructured":"Alves, G. et al. Incidence of Parkinson\u2019s disease in Norway: the Norwegian ParkWest study. J. Neurol. Neurosurg. Psychiatry 80, 851\u2013857 (2009).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"768_CR25","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","volume":"55","author":"AJ Hughes","year":"1992","unstructured":"Hughes, A. J., Daniel, S. E., Kilford, L. & Lees, A. J. Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55, 181\u2013184 (1992).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"768_CR26","first-page":"153","volume":"2","author":"S Fahn","year":"1987","unstructured":"Fahn, S. Unified Parkinson\u2019s disease rating scale. Recent Dev. Parkinsons Dis. 2, 153\u2013163 (1987).","journal-title":"Recent Dev. Parkinsons Dis."},{"key":"768_CR27","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1212\/WNL.17.5.427","volume":"17","author":"MM Hoehn","year":"1967","unstructured":"Hoehn, M. M. & Yahr, M. D. Parkinsonism: onset, progression and mortality. Neurology 17, 427\u2013442 (1967).","journal-title":"Neurology"},{"key":"768_CR28","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. \u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189\u2013198 (1975).","journal-title":"J. Psychiatr. Res."},{"key":"768_CR29","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/ane.12977","volume":"138","author":"K Herlofson","year":"2018","unstructured":"Herlofson, K. et al. Inflammation and fatigue in early, untreated Parkinson\u2019s Disease. Acta Neurol. Scand. 138, 394\u2013399 (2018).","journal-title":"Acta Neurol. Scand."},{"key":"768_CR30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ebiom.2015.11.036","volume":"3","author":"M Gissl\u00e9n","year":"2016","unstructured":"Gissl\u00e9n, M. et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 3, 135\u2013140 (2016).","journal-title":"EBioMedicine"},{"key":"768_CR31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1159\/000365637","volume":"43","author":"V Philipps","year":"2014","unstructured":"Philipps, V. et al. Normalized mini-mental state examination for assessing cognitive change in population-based brain aging studies. Neuroepidemiology 43, 15\u201325 (2014).","journal-title":"Neuroepidemiology"}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-024-00768-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-024-00768-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-024-00768-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T11:33:14Z","timestamp":1724412794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-024-00768-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,21]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["768"],"URL":"https:\/\/doi.org\/10.1038\/s41531-024-00768-1","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,21]]},"assertion":[{"value":"26 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.C.P. is supported by HELSEVEST (29604). A.U. and O.B.T. report no disclosures relevant to the manuscript. G.A. and J.M.-G. are supported by the Research Council of Norway (287842). K.B. has served as a consultant at advisory boards, or on data monitoring committees, for Abcam, Axon, BioArctic, Biogen, Eisai, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. K.B. is supported by the Swedish Research Council (#2017\u201300915 and #2022\u201300732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270, and #AF-994551), Hj\u00e4rnfonden, Sweden (#FO2017\u20130243 and #ALZ2022\u20130006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019\u2013466\u2013236), the Alzheimer\u2019s Association 2021 Zenith Award (ZEN-21\u2013848495), the Alzheimer\u2019s Association 2022\u20132025 Grant (SG-23\u20131038904 QC), La Fondation Recherche Alzheimer (FRA), Paris, France, and the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark. H.Z. has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2023\u201300356; #2022\u201301018 and #2019\u201302397), the European Union\u2019s Horizon Europe research and innovation programme under grant agreement No. 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809\u20132016862), the AD Strategic Fund and the Alzheimer\u2019s Association (#ADSF-21\u2013831376-C, #ADSF-21\u2013831381-C, and #ADSF-21\u2013831377-C), the Bluefield Project, Cure Alzheimer\u2019s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen f\u00f6r Gamla Tj\u00e4narinnor, Hj\u00e4rnfonden, Sweden (#FO2022\u20130270), the European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement No. 860197 (MIRIADE), the European Union Joint Programme\u2013Neurodegenerative Disease Research (JPND2021\u201300694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). J.M.-G. and J.L. are supported by the Norwegian Health Association (16152).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"162"}}