{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:17:53Z","timestamp":1792801073611,"version":"4.5.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1038\/s41591-026-04212-0","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:02:37Z","timestamp":1771236157000},"page":"1073-1084","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-7789","authenticated-orcid":false,"given":"Katharina","family":"Bolsewig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5650","authenticated-orcid":false,"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-116X","authenticated-orcid":false,"given":"Yanaika S.","family":"Hok-A-Hin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane","family":"Al Idrissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-6384","authenticated-orcid":false,"given":"Lisa","family":"Vermunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-5478","authenticated-orcid":false,"given":"Alberto","family":"Lle\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-3245","authenticated-orcid":false,"given":"Daniel","family":"Alcolea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Sieben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0304-9785","authenticated-orcid":false,"given":"Sebastiaan","family":"Engelborghs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5461-162X","authenticated-orcid":false,"given":"Anja Hviid","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen G.","family":"Hasselbalch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjado H. J.","family":"Morrema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J. M.","family":"Hoozemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G. J. M.","family":"Bol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"van Alphen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-3258","authenticated-orcid":false,"given":"Davide","family":"Chiasserini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Paolini Paoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-3967","authenticated-orcid":false,"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-455X","authenticated-orcid":false,"given":"Young-gun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-4428","authenticated-orcid":false,"given":"Suhee","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahreum","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-3352","authenticated-orcid":false,"given":"Seun","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Seok","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"del Campo Mil\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-6224","authenticated-orcid":false,"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-5357","authenticated-orcid":false,"given":"Wilma D. J.","family":"van de Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afina W.","family":"Lemstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-4243","authenticated-orcid":false,"given":"Eline A. J.","family":"Willemse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"4212_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ncl.2017.01.004","volume":"35","author":"D Galasko","year":"2017","unstructured":"Galasko, D. Lewy body disorders. Neurol. Clin. 35, 325\u2013338 (2017).","journal-title":"Neurol. Clin."},{"key":"4212_CR2","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S1474-4422(23)00405-2","volume":"23","author":"T Simuni","year":"2024","unstructured":"Simuni, T. et al. A biological definition of neuronal alpha-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 23, 178\u2013190 (2024).","journal-title":"Lancet Neurol."},{"key":"4212_CR3","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S1474-4422(23)00404-0","volume":"23","author":"GU Hoglinger","year":"2024","unstructured":"Hoglinger, G. U. et al. A biological classification of Parkinson\u2019s disease: the SynNeurGe research diagnostic criteria. Lancet Neurol. 23, 191\u2013204 (2024).","journal-title":"Lancet Neurol."},{"key":"4212_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120660","volume":"449","author":"M Okitsu","year":"2023","unstructured":"Okitsu, M. et al. Degeneration of nigrostriatal dopaminergic neurons in the early to intermediate stage of dementia with Lewy bodies and Parkinson\u2019s disease. J. Neurol. Sci. 449, 120660 (2023).","journal-title":"J. Neurol. Sci."},{"key":"4212_CR5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00401-010-0711-0","volume":"120","author":"WJ Schulz-Schaeffer","year":"2010","unstructured":"Schulz-Schaeffer, W. J. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson\u2019s disease and Parkinson\u2019s disease dementia. Acta Neuropathol. 120, 131\u2013143 (2010).","journal-title":"Acta Neuropathol."},{"key":"4212_CR6","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma, R. B. et al. MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov. Disord. 30, 1591\u20131601 (2015.","journal-title":"Mov. Disord."},{"key":"4212_CR7","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","volume":"89","author":"IG McKeith","year":"2017","unstructured":"McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89, 88\u2013100 (2017).","journal-title":"Neurology"},{"key":"4212_CR8","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/ageing\/afi190","volume":"34","author":"J Zaccai","year":"2005","unstructured":"Zaccai, J., McCracken, C. & Brayne, C. A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 34, 561\u2013566 (2005).","journal-title":"Age Ageing"},{"key":"4212_CR9","doi-asserted-by":"publisher","first-page":"S18","DOI":"10.1002\/mdc3.13753","volume":"10","author":"B Mollenhauer","year":"2023","unstructured":"Mollenhauer, B. Status of current biofluid biomarkers in Parkinson\u2019s disease. Mov. Disord. Clin. Pract. 10, S18\u2013S20 (2023).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"4212_CR10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s00401-023-02663-0","volume":"147","author":"GM Bentivenga","year":"2024","unstructured":"Bentivenga, G. M. et al. Performance of a seed amplification assay for misfolded alpha-synuclein in cerebrospinal fluid and brain tissue in relation to Lewy body disease stage and pathology burden. Acta Neuropathol. 147, 18 (2024).","journal-title":"Acta Neuropathol."},{"key":"4212_CR11","doi-asserted-by":"publisher","first-page":"e930","DOI":"10.1212\/WNL.0000000000012438","volume":"97","author":"M Rossi","year":"2021","unstructured":"Rossi, M. et al. Diagnostic value of the CSF alpha-synuclein real-time quaking-induced conversion assay at the prodromal mci stage of dementia with Lewy bodies. Neurology 97, e930\u2013e940 (2021).","journal-title":"Neurology"},{"key":"4212_CR12","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1002\/alz.13658","volume":"20","author":"G Bellomo","year":"2024","unstructured":"Bellomo, G. et al. Investigating alpha-synuclein co-pathology in Alzheimer\u2019s disease by means of cerebrospinal fluid alpha-synuclein seed amplification assay. Alzheimers Dement. 20, 2444\u20132452 (2024).","journal-title":"Alzheimers Dement."},{"key":"4212_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52299-1","volume":"15","author":"LE Collij","year":"2024","unstructured":"Collij, L. E. et al. Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer\u2019s disease. Nat. Commun. 15, 8061 (2024).","journal-title":"Nat. Commun."},{"key":"4212_CR14","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/S1474-4422(07)70057-1","volume":"6","author":"I McKeith","year":"2007","unstructured":"McKeith, I. et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 6, 305\u2013313 (2007).","journal-title":"Lancet Neurol."},{"key":"4212_CR15","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/1531-8257(200005)15:3<503::AID-MDS1013>3.0.CO;2-V","volume":"15","author":"TS Benamer","year":"2000","unstructured":"Benamer, T. S. et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov. Disord. 15, 503\u2013510 (2000).","journal-title":"Mov. Disord."},{"key":"4212_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41122-y","volume":"14","author":"M Del Campo","year":"2023","unstructured":"Del Campo, M. et al. CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer s disease. Nat. Commun. 14, 5635 (2023).","journal-title":"Nat. Commun."},{"key":"4212_CR17","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1038\/s43587-023-00478-y","volume":"3","author":"JB Pereira","year":"2023","unstructured":"Pereira, J. B. et al. DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease. Nat. Aging 3, 1201\u20131209 (2023).","journal-title":"Nat. Aging"},{"key":"4212_CR18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-023-00374-w","volume":"12","author":"W Paslawski","year":"2023","unstructured":"Paslawski, W. et al. Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson\u2019s disease. Transl. Neurodegener. 12, 42 (2023).","journal-title":"Transl. Neurodegener."},{"key":"4212_CR19","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s00401-024-02706-0","volume":"147","author":"J Rutledge","year":"2024","unstructured":"Rutledge, J. et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson\u2019s disease. Acta Neuropathol. 147, 52 (2024).","journal-title":"Acta Neuropathol."},{"key":"4212_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.abb.2013.12.020","volume":"546","author":"M Bertoldi","year":"2014","unstructured":"Bertoldi, M. Mammalian DOPA decarboxylase: structure, catalytic activity and inhibition. Arch. Biochem. Biophys. 546, 1\u20137 (2014).","journal-title":"Arch. Biochem. Biophys."},{"key":"4212_CR21","doi-asserted-by":"publisher","first-page":"114367","DOI":"10.1016\/j.bbr.2023.114367","volume":"445","author":"O Hsam","year":"2023","unstructured":"Hsam, O. & Kohl, Z. Serotonin in synucleinopathies. Behav. Brain Res. 445, 114367 (2023).","journal-title":"Behav. Brain Res."},{"key":"4212_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56293-z","volume":"16","author":"K Bolsewig","year":"2025","unstructured":"Bolsewig, K. et al. Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment. Nat. Commun. 16, 1139 (2025).","journal-title":"Nat. Commun."},{"key":"4212_CR23","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40035-024-00421-0","volume":"13","author":"E Appleton","year":"2024","unstructured":"Appleton, E. et al. DOPA-decarboxylase is elevated in CSF, but not plasma, in prodromal and de novo Parkinson\u2019s disease. Transl. Neurodegener. 13, 31 (2024).","journal-title":"Transl. Neurodegener."},{"key":"4212_CR24","doi-asserted-by":"publisher","unstructured":"Aviolat, H., Mollon, J., Giaisi, S., Barghorn, S. & Heym, R. G. A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic and prognostic biomarker for Parkinson\u2019s disease. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2025.02.26.25322938 (2025).","DOI":"10.1101\/2025.02.26.25322938"},{"key":"4212_CR25","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3389\/fneur.2015.00179","volume":"6","author":"U Andreasson","year":"2015","unstructured":"Andreasson, U. et al. A practical guide to immunoassay method validation. Front. Neurol. 6, 179 (2015).","journal-title":"Front. Neurol."},{"key":"4212_CR26","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/ane.13028","volume":"139","author":"R Savica","year":"2019","unstructured":"Savica, R. et al. Lewy body pathology in Alzheimer\u2019s disease: a clinicopathological prospective study. Acta Neurol. Scand. 139, 76\u201381 (2019).","journal-title":"Acta Neurol. Scand."},{"key":"4212_CR27","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/brain\/awaa438","volume":"144","author":"JL Robinson","year":"2021","unstructured":"Robinson, J. L. et al. The development and convergence of co-pathologies in Alzheimer\u2019s disease. Brain 144, 953\u2013962 (2021).","journal-title":"Brain"},{"key":"4212_CR28","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure, M. A. & Dickson, D. W. The neuropathological diagnosis of Alzheimer\u2019s disease. Mol. Neurodegener. 14, 32 (2019).","journal-title":"Mol. Neurodegener."},{"key":"4212_CR29","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1212\/CON.0000000000000348","volume":"22","author":"NR McFarland","year":"2016","unstructured":"McFarland, N. R. Diagnostic approach to atypical Parkinsonian syndromes. Continuum 22, 1117\u20131142 (2016).","journal-title":"Continuum"},{"key":"4212_CR30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00401-020-02160-8","volume":"140","author":"M Rossi","year":"2020","unstructured":"Rossi, M. et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol. 140, 49\u201362 (2020).","journal-title":"Acta Neuropathol."},{"key":"4212_CR31","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/ana.25447","volume":"85","author":"A van Rumund","year":"2019","unstructured":"van Rumund, A. et al. alpha-Synuclein real-time quaking-induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism. Ann. Neurol. 85, 777\u2013781 (2019).","journal-title":"Ann. Neurol."},{"key":"4212_CR32","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1002\/acn3.50897","volume":"6","author":"M Bongianni","year":"2019","unstructured":"Bongianni, M. et al. alpha-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies. Ann. Clin. Transl. Neurol. 6, 2120\u20132126 (2019).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"4212_CR33","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1093\/ijnp\/pyx056","volume":"20","author":"P Belujon","year":"2017","unstructured":"Belujon, P. & Grace, A. A. Dopamine system dysregulation in major depressive disorders. Int. J. Neuropsychopharmacol. 20, 1036\u20131046 (2017).","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"4212_CR34","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1002\/mds.29835","volume":"39","author":"S Khosousi","year":"2024","unstructured":"Khosousi, S. et al. Increased CSF DOPA decarboxylase correlates with lower DaT-SPECT binding: analyses in Biopark and PPMI cohorts. Mov. Disord. 39, 1881\u20131885 (2024).","journal-title":"Mov. Disord."},{"key":"4212_CR35","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1212\/01.WNL.0000123248.39847.1D","volume":"62","author":"Z Walker","year":"2004","unstructured":"Walker, Z. et al. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology 62, 1568\u20131572 (2004).","journal-title":"Neurology"},{"key":"4212_CR36","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13195-014-0052-7","volume":"6","author":"M Marquie","year":"2014","unstructured":"Marquie, M. et al. Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an (11)C altropane positron emission tomography study. Alzheimers Res. Ther. 6, 52 (2014).","journal-title":"Alzheimers Res. Ther."},{"key":"4212_CR37","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1111\/j.1471-4159.2006.04146.x","volume":"99","author":"R Tehranian","year":"2006","unstructured":"Tehranian, R., Montoya, S. E., Van Laar, A. D., Hastings, T. G. & Perez, R. G. Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. J. Neurochem. 99, 1188\u20131196 (2006).","journal-title":"J. Neurochem."},{"key":"4212_CR38","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1097\/01.jnen.0000230520.47768.1a","volume":"65","author":"F Mori","year":"2006","unstructured":"Mori, F. et al. Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J. Neuropathol. Exp. Neurol. 65, 808\u2013815 (2006).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"4212_CR39","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1016\/j.neubiorev.2013.07.001","volume":"37","author":"M Catani","year":"2013","unstructured":"Catani, M., Dell\u2019acqua, F. & Thiebaut de Schotten, M. A revised limbic system model for memory, emotion and behaviour. Neurosci. Biobehav. Rev. 37, 1724\u20131737 (2013).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"4212_CR40","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nature12654","volume":"503","author":"KD Harris","year":"2013","unstructured":"Harris, K. D. & Mrsic-Flogel, T. D. Cortical connectivity and sensory coding. Nature 503, 51\u201358 (2013).","journal-title":"Nature"},{"key":"4212_CR41","volume":"15","author":"AHYS Hok","year":"2023","unstructured":"Hok, A. H. Y. S. et al. Thimet oligopeptidase as a potential CSF biomarker for Alzheimer\u2019s disease: a cross-platform validation study. Alzheimers Dement. 15, e12456 (2023).","journal-title":"Alzheimers Dement."},{"key":"4212_CR42","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.3233\/JAD-220323","volume":"88","author":"AL Wojdala","year":"2022","unstructured":"Wojdala, A. L. et al. Phosphatidylethanolamine binding protein 1 (PEBP1) in Alzheimer\u2019s disease: ELISA development and clinical validation. J. Alzheimers Dis. 88, 1459\u20131468 (2022).","journal-title":"J. Alzheimers Dis."},{"key":"4212_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02796-9","volume":"20","author":"AHYS Hok","year":"2023","unstructured":"Hok, A. H. Y. S. et al. Neuroinflammatory CSF biomarkers MIF, sTREM1, and sTREM2 show dynamic expression profiles in Alzheimer\u2019s disease. J. Neuroinflammation 20, 107 (2023).","journal-title":"J. Neuroinflammation"},{"key":"4212_CR44","doi-asserted-by":"crossref","unstructured":"World Medical Association World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 2191\u20132194 (2013).","DOI":"10.1001\/jama.2013.281053"},{"key":"4212_CR45","first-page":"597","volume":"5","author":"D Alcolea","year":"2019","unstructured":"Alcolea, D. et al. The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: a data set for biomarker discovery and validation in neurodegenerative disorders. Alzheimers Dement. 5, 597\u2013609 (2019).","journal-title":"Alzheimers Dement."},{"key":"4212_CR46","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr.","year":"2018","unstructured":"Jack, C. R. Jr. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 14, 535\u2013562 (2018).","journal-title":"Alzheimers Dement."},{"key":"4212_CR47","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.neurobiolaging.2018.08.007","volume":"72","author":"YG Lee","year":"2018","unstructured":"Lee, Y. G. et al. Amyloid-\u03b2-related and unrelated cortical thinning in dementia with Lewy bodies. Neurobiol. Aging 72, 32\u201339 (2018).","journal-title":"Neurobiol. Aging"},{"key":"4212_CR48","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1373\/clinchem.2009.130518","volume":"56","author":"C Mulder","year":"2010","unstructured":"Mulder, C. et al. Amyloid-beta(1\u201342), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin. Chem. 56, 248\u2013253 (2010).","journal-title":"Clin. Chem."},{"key":"4212_CR49","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1373\/clinchem.2017.281055","volume":"64","author":"BM Tijms","year":"2018","unstructured":"Tijms, B. M. et al. Unbiased approach to counteract upward drift in cerebrospinal fluid amyloid-beta 1\u201342 analysis results. Clin. Chem. 64, 576\u2013585 (2018).","journal-title":"Clin. Chem."},{"key":"4212_CR50","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1002\/acn3.50873","volume":"6","author":"D Alcolea","year":"2019","unstructured":"Alcolea, D. et al. Agreement of amyloid PET and CSF biomarkers for Alzheimer\u2019s disease on Lumipulse. Ann. Clin. Transl. Neurol. 6, 1815\u20131824 (2019).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"4212_CR51","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3233\/JAD-151097","volume":"54","author":"C Somers","year":"2016","unstructured":"Somers, C. et al. A decade of cerebrospinal fluid biomarkers for Alzheimer's disease in Belgium. J. Alzheimers Dis. 54, 383\u2013395 (2016).","journal-title":"J. Alzheimers Dis."},{"key":"4212_CR52","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.3233\/JAD-201506","volume":"81","author":"AH Simonsen","year":"2021","unstructured":"Simonsen, A. H., Musaeus, C. S., Christensen, G. L., Hasselbalch, S. G. & Waldemar, G. Upwards drift of cerebrospinal fluid amyloid-beta 42 over twelve years in a consecutive clinical cohort. J. Alzheimers Dis. 81, 1369\u20131373 (2021).","journal-title":"J. Alzheimers Dis."},{"key":"4212_CR53","doi-asserted-by":"publisher","first-page":"647783","DOI":"10.3389\/fnins.2021.647783","volume":"15","author":"G Bellomo","year":"2021","unstructured":"Bellomo, G. et al. Machine learning driven profiling of cerebrospinal fluid core biomarkers in Alzheimer\u2019s disease and other neurological disorders. Front. Neurosci. 15, 647783 (2021).","journal-title":"Front. Neurosci."},{"key":"4212_CR54","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","volume":"7","author":"MS Albert","year":"2011","unstructured":"Albert, M. S. et al. The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 7, 270\u2013279 (2011).","journal-title":"Alzheimers Dement."},{"key":"4212_CR55","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann, G. M. et al. 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. Alzheimers Dement. 7, 263\u2013269 (2011).","journal-title":"Alzheimers Dement."},{"key":"4212_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine, T. J. et al. National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol. 123, 1\u201311 (2012).","journal-title":"Acta Neuropathol."},{"key":"4212_CR57","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1212\/01.wnl.0000187889.17253.b1","volume":"65","author":"IG McKeith","year":"2005","unstructured":"McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65, 1863\u20131872 (2005).","journal-title":"Neurology"},{"key":"4212_CR58","doi-asserted-by":"publisher","first-page":"101771","DOI":"10.1016\/j.nicl.2019.101771","volume":"22","author":"J Ottoy","year":"2019","unstructured":"Ottoy, J. et al. Association of short-term cognitive decline and MCI-to-AD dementia conversion with CSF, MRI, amyloid- and (18)F-FDG-PET imaging. Neuroimage Clin. 22, 101771 (2019).","journal-title":"Neuroimage Clin."},{"key":"4212_CR59","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1111\/j.1750-3639.2008.00147.x","volume":"18","author":"I Alafuzoff","year":"2008","unstructured":"Alafuzoff, I. et al. Staging of neurofibrillary pathology in Alzheimer\u2019s disease: a study of the BrainNet Europe Consortium. Brain Pathol. 18, 484\u2013496 (2008).","journal-title":"Brain Pathol."},{"key":"4212_CR60","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00401-009-0523-2","volume":"117","author":"I Alafuzoff","year":"2009","unstructured":"Alafuzoff, I. et al. Staging\/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol. 117, 635\u2013652 (2009).","journal-title":"Acta Neuropathol."},{"key":"4212_CR61","unstructured":"R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing: Vienna, Austria https:\/\/www.R-project.org\/ (2020)."},{"key":"4212_CR62","unstructured":"Grosjean, P. & Ibanez, F. pastecs: package for analysis of space-time ecological series. R package version 1.3 (2018)."},{"key":"4212_CR63","unstructured":"Fox, J. & Weisberg, S. An R Companion to Applied Regression (Sage, 2019)."},{"key":"4212_CR64","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","volume":"12","author":"X Robin","year":"2011","unstructured":"Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011).","journal-title":"BMC Bioinformatics"},{"key":"4212_CR65","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/ebmental-2019-300117","volume":"22","author":"S Balduzzi","year":"2019","unstructured":"Balduzzi, S., Rucker, G. & Schwarzer, G. How to perform a meta-analysis with R: a practical tutorial. Evid. Based Ment. Health 22, 153\u2013160 (2019).","journal-title":"Evid. Based Ment. Health"},{"key":"4212_CR66","unstructured":"Potapov, S. et al. MCR: method comparison regression. https:\/\/CRAN.R-project.org\/package=mcr\/ (2023)."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04212-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04212-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04212-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:03:01Z","timestamp":1774018981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04212-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,16]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["4212"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04212-0","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,16]]},"assertion":[{"value":"21 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.B. received a one-time consulting fee from Fujirebio paid to the institution in 2025. G.B. received honoraria from Fujirebio and completed paid consultancies for Parkinson\u2019s Foundation. G.B. received travel\/educational grants from Fujirebio and Alzheimer\u2019s Association. A. Lle\u00f3 has received fees for advisory board meetings from Biogen, Beckman Coulter, Eisai, Fujirebio-Europe, Grifols, Lilly, Novartis, Roche, Otsuka Pharmaceutical, Nutricia, Zamb\u00f3n and Novo Nordisk. A. Lle\u00f3 has received speaker honoraria from Lilly, Biogen, KRKA, Novo Nordisk, Nutricia and Zambon. A. Lle\u00f3 is inventor of a patent on markers of synaptopathy in neurodegenerative disease (WO2019175379A1, Licensed to ADx) and on a patent antibody for amyloid precursor, methods and uses thereof (European priority N\u00b0EP25382226: priority date 12 Mar 2025). D.A. participated in advisory boards from Fujirebio-Europe, Roche Diagnostics, Grifols S.A. and Lilly, and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Krka Farmac\u00e9utica S.L., Zambon S.A.U., Neuraxpharm, Alter Medica, Lilly and Esteve Pharmaceuticals S.A. S.E. has received consulting fees from Biogen (paid to institution), Eisai (paid to institution), Icometrix (paid to institution), Janssen (paid to institution), Eli Lilly, Novartis (paid to institution) and Remynd (paid to institution). S.E. holds patent EP3452830B1 for an assay for the diagnosis of a neurological disease (licensed to ADx Neurosciences NV & Euroimmun Medizinische Labordiagnostika AG). S.E. is a member of SMB\/SAB for EU-H2020 project RECAGE and of the DSMB of PRImus-AD. A.H.S. received a one-time consulting fee from EISAI\/BioArctic paid to the institution in 2025. As of 01 Jul 2024, J.J.M.H. is employed by F. Hoffmann-La Roche. Before 01 Jul 2024, J.J.M.H. received grants from the Dutch Research Council (ZonMW) and Alzheimer Netherlands, performed contract research, or received grants from Merck, ONO Pharmaceuticals, Janssen Prevention Center, Discoveric Bio, Axon Neurosciences, Roche, Genentech, Promis, Denali, FirstBiotherapeutics and Ensol Biosciences. All payments were made to the institution. J.J.M.H. participated in the scientific advisory board of Alzheimer Netherlands and has been editor-in-chief for Acta Neuropathologica Communications. L.G. has participated in advisory boards for, and received writing or speaker honoraria and travel grants from, Almirall, Biogen, Eisai, Euroimmun, Fujirebio, Lilly, Merck, Mylan, Novartis, Roche, Sanofi, Siemens Healthineers and Teva. D.C. has received travel\/educational grants from Fujirebio. L.P. served as Member of Advisory Boards for Fujirebio, IBL, Roche and Merck. M.d.C.M. has been an invited speaker at Eisai and Novo Nordisk and has been an invited writer for Springer Healthcare. M.d.C.M. is an associate editor at Alzheimer\u00b4s Research & Therapy and scientific advisor for the Michael J Fox Foundation. As of 01 Nov 2025, W.M.v.d.F. is executive director at Alzheimer Nederland, Amersfoort the Netherlands. Before 01 Nov 2025, research programs of W.M.v.d.F. have been funded by ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, Stichting Dioraphte, Noaber foundation, Pieter Houbolt Fonds, Gieskes-Strijbis fonds, Stichting Equilibrio, Edwin Bouw fonds, Pasman Stichting, Philips, Biogen MA, Novartis-NL, Life-MI, AVID, Roche BV, Eli Lilly-NL, Fujifilm, Eisai and Combinostics. W.M.v.d.F. is a recipient of ABOARD, which is a public\u2013private partnership receiving funding from ZonMW (73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; LSHM20106). Before 01 Nov 2025, W.M.v.d.F. has been an invited speaker at Biogen MA, Danone, Eisai, WebMD Neurology (Medscape), Novo Nordisk, Springer Healthcare and the European Brain Council. W.M.v.d.F. has been consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA, Eisai, Eli Lilly, Owkin France and Nationale Nederlanden Ventures. W.M.v.d.F. has participated in advisory boards of Biogen MA, Roche and Eli Lilly. All funding has been paid to Amsterdam UMC. In 2024\u20132025, W.M.v.d.F. has been a member of the steering committee of phase 3 EVOKE\/EVOKE+ studies (Novo Nordisk). In 2025, W.M.v.d.F. has been a member of the steering committee of a phase 3 trontinemab study (Roche). All funding has been paid to Amsterdam UMC. W.M.v.d.F. was associate editor of Alzheimer, Research & Therapy in 2020\/2021. W.M.v.d.F. was associate editor at Brain 2021\u20132025. W.M.v.d.F. is chair of the Scientific Leadership Group of InRAD. W.M.v.d.F. is a member of the Supervisory Board (Raad van Toezicht) at Trimbos Instituut. W.D.J.v.d.B. was financially supported by grants from the Dutch Research council (ZonMW 70-73305-98-106; 70-73305-98-102), Alzheimer association (AARF-18-566459), The Michael J. Fox foundation (MJFF-022468; MJFF027187), Parkinson Association (2020-G01), Stichting Woelse Waard (ParKCODE; Nederlands Parkinson Cohort), Horizon Europe (NEUROCOV) and Parkinson Foundation (PF-TRAIL-144386). W.D.J.v.d.B. co-leads \u2018ProPARK\u2019, a public\u2013private partnership receiving funding from ZonMW (40-46000-98-101), Hersenstichting, Parkinson Vereniging, PHARMO Institute NV, Stichting Woelse Waard, Stichting Alkemade-Keuls fonds, CHDR, ABBVIE, Hoffman-La Roche and OccamzRazor. W.D.J.v.d.B. received funding for a public\u2013private partnership \u2018CONCERT\u2019 and \u2018ADAPT-PD\u2019 from Health~Holland, Topsector Life Sciences & Health in collaboration with Roche and Genentech. W.D.J.v.d.B. performed contract research for Roche Tissue Diagnostics, Discoveric Bio, AC Immune and Gain Therapeutics. All funding has been paid to Amsterdam UMC. W.D.J.v.d.B. is a member of the scientific advisory board of Gain Therapeutics and Alzheimer Nederland. W.D.J.v.d.B. is the president of the Dutch association for Parkinson Scientists and member of the board of the Parkinsonalliance Netherlands. As of 01 Nov 2025, E.A.J.W. is a contractor for Roche Diagnostics International. C.E.T. has research contracts with Acumen, ADx Neurosciences, AC Immune, Alamar, Aribio, Axon Neurosciences, Beckman Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, C2N diagnostics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Instant Nano Biosensors, Merck, Muna, Nitrase Therapeutics, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Sysmex, Toyama, Vaccinex and Vivoryon. C.E.T. is editor-in-chief of Alzheimer Research and Therapy, serves on the editorial boards of Molecular Neurodegeneration, Alzheimer\u2019s & Dementia, Neurology: Neuroimmunology & Neuroinflammation, and MedidactNeurologie\/Springer, and is a member of the committee to define guidelines for cognitive disturbances and a committee for acute neurology in the Netherlands. C.E.T. has contracts with Aribio, Biogen, Beckman Coulter, Cognition Therapeutics, Danaher, Eisai, Eli Lilly, Janssen, Merck, Neurogen Biomarking, Nordic Biosciences, Novo Nordisk, Novartis, Olink, Quanterix, Roche, Sanofi and Veravas. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}