{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:24:29Z","timestamp":1786965869631,"version":"build-2736575974"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2025-02319"],"award-info":[{"award-number":["2025-02319"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Alzheimer Foundation","award":["AF-1011799"],"award-info":[{"award-number":["AF-1011799"]}]},{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["ADG-101096455"],"award-info":[{"award-number":["ADG-101096455"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["ZEN24-1069572"],"award-info":[{"award-number":["ZEN24-1069572"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["ALZSI-26-1523522"],"award-info":[{"award-number":["ALZSI-26-1523522"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut and Alice Wallenberg Foundation","doi-asserted-by":"crossref","award":["2022-0231"],"award-info":[{"award-number":["2022-0231"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University"},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"crossref","award":["FO2025-0055"],"award-info":[{"award-number":["FO2025-0055"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Parkinson foundation of Sweden","award":["1412\/22"],"award-info":[{"award-number":["1412\/22"]}]},{"name":"Familjen R\u00f6nnstr\u00f6ms Stiftelse"},{"name":"WASP and DDLS Joint call for research projects","award":["WASP\/DDLS22-066"],"award-info":[{"award-number":["WASP\/DDLS22-066"]}]},{"name":"Michael J Fox Foundation","award":["MJFF-025507"],"award-info":[{"award-number":["MJFF-025507"]}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006129","name":"Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sk\u00e5ne University Hospital Foundation","award":["2020-O000028"],"award-info":[{"award-number":["2020-O000028"]}]},{"name":"Global Research and Imaging Platform"},{"name":"Regionalt Forskningsst\u00f6d"},{"name":"Swedish federal government under the ALF agreement","award":["2022-Projekt0107"],"award-info":[{"award-number":["2022-Projekt0107"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2026,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brain amyloid-\u03b2 (A\u03b2) pathology is a core feature of Alzheimer disease (AD) and can be quantified using positron emission tomography (PET). Cerebrospinal fluid (CSF) and plasma biomarkers detect abnormal A\u03b2, but it is unclear to what degree they can predict quantitative A\u03b2-PET. We explored plasma and CSF biomarkers in relation to A\u03b2-PET in the BioFINDER-2 study (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091053), and the BioFINDER-1 study (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009238). We developed a machine learning pipeline to predict A\u03b2-PET using CSF and plasma measures. The best models achieved R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.79. Plasma P-tau217 and CSF A\u03b242\/A\u03b240 contributed the most. CSF A\u03b242\/A\u03b240 contributed most to identify A\u03b2-positivity, while continuous A\u03b2-PET load within the positive range was best predicted by plasma P-tau217. Models using only plasma measures approached performance of CSF models. Altered metabolism of soluble A\u03b2 may be highly associated with presence of A\u03b2 plaques, while soluble P-tau217 levels may continue to change during build-up of A\u03b2 pathology.\n                  <\/jats:p>","DOI":"10.1038\/s44321-025-00348-7","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:05:39Z","timestamp":1764590739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prediction of continuous amyloid positron emission tomography with fluid measures of phosphorylated tau and \u03b2-amyloid"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-7724","authenticated-orcid":false,"given":"Niklas","family":"Mattsson-Carlgren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-772X","authenticated-orcid":false,"given":"Linda","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1702","authenticated-orcid":false,"given":"Randall J","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Barthelemy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-1930","authenticated-orcid":false,"given":"Sebastian","family":"Palmqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-7286","authenticated-orcid":false,"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"348_CR1","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/s41591-022-02074-w","volume":"28","author":"NJ Ashton","year":"2022","unstructured":"Ashton NJ, Janelidze S, Mattsson-Carlgren N, Binette AP, Strandberg O, Brum WS, Karikari TK, Gonz\u00e1lez-Ortiz F, Di Molfetta G, Meda FJ et al (2022) Differential roles of A\u03b242\/40, p-tau231 and p-tau217 for Alzheimer\u2019s trial selection and disease monitoring. Nat Med 28:2555\u20132562","journal-title":"Nat Med"},{"key":"348_CR2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","volume":"141","author":"NJ Ashton","year":"2021","unstructured":"Ashton NJ, Pascoal TA, Karikari TK, Benedet AL, Lantero-Rodriguez J, Brinkmalm G, Snellman A, Sch\u00f6ll M, Troakes C, Hye A et al (2021) Plasma p-tau231: a new biomarker for incipient Alzheimer\u2019s disease pathology. Acta Neuropathol ((Berl)) 141:709\u2013724","journal-title":"Acta Neuropathol ((Berl))"},{"key":"348_CR3","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20200861","volume":"217","author":"NR Barth\u00e9lemy","year":"2020","unstructured":"Barth\u00e9lemy NR, Horie K, Sato C, Bateman RJ (2020) Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer\u2019s disease. J Exp Med 217:e20200861","journal-title":"J Exp Med"},{"key":"348_CR4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s43587-023-00380-7","volume":"3","author":"NR Barth\u00e9lemy","year":"2023","unstructured":"Barth\u00e9lemy NR, Saef B, Li Y, Gordon BA, He Y, Horie K, Stomrud E, Salvad\u00f3 G, Janelidze S, Sato C et al (2023) CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer\u2019s disease. Nat Aging 3:391\u2013401","journal-title":"Nat Aging"},{"key":"348_CR5","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/s41591-024-02869-z","volume":"30","author":"NR Barth\u00e9lemy","year":"2024","unstructured":"Barth\u00e9lemy NR, Salvad\u00f3 G, Schindler SE, He Y, Janelidze S, Collij LE, Saef B, Henson RL, Chen CD, Gordon BA et al (2024) Highly accurate blood test for Alzheimer\u2019s disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med 30:1085\u20131095","journal-title":"Nat Med"},{"key":"348_CR6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s13195-022-01117-1","volume":"14","author":"AL Brand","year":"2022","unstructured":"Brand AL, Lawler PE, Bollinger JG, Li Y, Schindler SE, Li M, Lopez S, Ovod V, Nakamura A, Shaw LM et al (2022) The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer\u2019s disease: a literature review. Alzheimers Res Ther 14:195","journal-title":"Alzheimers Res Ther"},{"key":"348_CR7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jama.2010.2008","volume":"305","author":"CM Clark","year":"2011","unstructured":"Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML et al (2011) Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 305:275\u2013283","journal-title":"JAMA"},{"key":"348_CR8","doi-asserted-by":"crossref","first-page":"5617","DOI":"10.1002\/alz.14073","volume":"20","author":"V Devanarayan","year":"2024","unstructured":"Devanarayan V, Doherty T, Charil A, Sachdev P, Ye Y, Murali LK, Llano DA, Zhou J, Reyderman L, Hampel H et al (2024) Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer\u2019s disease. Alzheimers Dement 20:5617\u20135628","journal-title":"Alzheimers Dement"},{"key":"348_CR9","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1001\/jamaneurol.2014.803","volume":"71","author":"MC Donohue","year":"2014","unstructured":"Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, Weiner M, Aisen PS, Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing, Alzheimer\u2019s Disease Neuroimaging Initiative et al (2014) The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol 71:961\u2013970","journal-title":"JAMA Neurol"},{"key":"348_CR10","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.bbi.2024.08.030","volume":"122","author":"C Fenoglio","year":"2024","unstructured":"Fenoglio C, Serpente M, Arcaro M, Carandini T, Sacchi L, Pintus M, Rotondo E, Borracci V, Ghezzi L, Bouzigues A et al (2024) Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study. Brain Behav Immun 122:231\u2013240","journal-title":"Brain Behav Immun"},{"key":"348_CR11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1515\/cclm-2021-0651","volume":"60","author":"J Gobom","year":"2022","unstructured":"Gobom J, Parnetti L, Rosa-Neto P, Vyhnalek M, Gauthier S, Cataldi S, Lerch O, Laczo J, Cechova K, Clarin M et al (2022) Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid. Clin Chem Lab Med 60:207\u2013219","journal-title":"Clin Chem Lab Med"},{"key":"348_CR12","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","volume":"27","author":"O Hansson","year":"2021","unstructured":"Hansson O (2021) Biomarkers for neurodegenerative diseases. Nat Med 27:954\u2013963","journal-title":"Nat Med"},{"key":"348_CR13","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-023-00403-3","volume":"3","author":"O Hansson","year":"2023","unstructured":"Hansson O, Blennow K, Zetterberg H, Dage J (2023) Blood biomarkers for Alzheimer\u2019s disease in clinical practice and trials. Nat Aging 3:506\u2013519","journal-title":"Nat Aging"},{"key":"348_CR14","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.jalz.2018.01.010","volume":"14","author":"O Hansson","year":"2018","unstructured":"Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski JQ, Bittner T, Lifke V, Corradini V, Eichenlaub U, Batrla R et al (2018) CSF biomarkers of Alzheimer\u2019s disease concord with amyloid-\u03b2 PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement 14:1470\u20131481","journal-title":"Alzheimers Dement"},{"key":"348_CR15","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1038\/s41591-023-02443-z","volume":"29","author":"K Horie","year":"2023","unstructured":"Horie K, Salvad\u00f3 G, Barth\u00e9lemy NR, Janelidze S, Li Y, He Y, Saef B, Chen CD, Jiang H, Strandberg O et al (2023) CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer\u2019s disease. Nat Med 29:1954\u20131963","journal-title":"Nat Med"},{"key":"348_CR16","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J et al (2018) NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement 14:535\u2013562","journal-title":"Alzheimers Dement"},{"key":"348_CR17","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1001\/jamaneurol.2024.2619","volume":"81","author":"S Janelidze","year":"2024","unstructured":"Janelidze S, Barth\u00e9lemy NR, Salvad\u00f3 G, Schindler SE, Palmqvist S, Mattsson-Carlgren N, Braunstein JB, Ovod V, Bollinger JG, He Y et al (2024) Plasma phosphorylated Tau 217 and A\u03b242\/40 to predict early brain A\u03b2 accumulation in people without cognitive impairment. JAMA Neurol 81:947\u2013957.e242619","journal-title":"JAMA Neurol"},{"key":"348_CR18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41591-020-0755-1","volume":"26","author":"S Janelidze","year":"2020","unstructured":"Janelidze S, Mattsson N, Palmqvist S, Smith R, Beach TG, Serrano GE, Chai X, Proctor NK, Eichenlaub U, Zetterberg H et al (2020) Plasma P-tau181 in Alzheimer\u2019s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer\u2019s dementia. Nat Med 26:379\u2013386","journal-title":"Nat Med"},{"key":"348_CR19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/alz.12395","volume":"18","author":"S Janelidze","year":"2022","unstructured":"Janelidze S, Palmqvist S, Leuzy A, Stomrud E, Verberk IMW, Zetterberg H, Ashton NJ, Pesini P, Sarasa L, Allu\u00e9 JA et al (2022) Detecting amyloid positivity in early Alzheimer\u2019s disease using combinations of plasma A\u03b242\/A\u03b240 and p-tau. Alzheimers Dement 18:283\u2013293","journal-title":"Alzheimers Dement"},{"key":"348_CR20","first-page":"1","volume":"78","author":"S Janelidze","year":"2021","unstructured":"Janelidze S, Teunissen CE, Zetterberg H, Allu\u00e9 JA, Sarasa L, Eichenlaub U, Bittner T, Ovod V, Verberk IMW, Toba K et al (2021) Head-to-head comparison of 8 plasma amyloid-\u03b2 42\/40 assays in Alzheimer disease. JAMA Neurol 78:1\u20138","journal-title":"JAMA Neurol"},{"key":"348_CR21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/acn3.274","volume":"3","author":"S Janelidze","year":"2016","unstructured":"Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, van Westen D, Stomrud E, Minthon L, Blennow K et al (2016) CSF A\u03b242\/A\u03b240 and A\u03b242\/A\u03b238 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 3:154\u2013165","journal-title":"Ann Clin Transl Neurol"},{"key":"348_CR22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1001\/jamaneurol.2021.5216","volume":"79","author":"WJ Jansen","year":"2022","unstructured":"Jansen WJ, Janssen O, Tijms BM, Vos SJB, Ossenkoppele R, Visser PJ, Amyloid Biomarker Study Group, Aarsland D, Alcolea D, Altomare D et al (2022) Prevalence estimates of amyloid abnormality across the Alzheimer disease clinical spectrum. JAMA Neurol 79:228\u2013243","journal-title":"JAMA Neurol"},{"key":"348_CR23","volume":"15","author":"L Karlsson","year":"2024","unstructured":"Karlsson L, Vogel J, Arvidsson I, \u00c5str\u00f6m K, Janelidze S, Blennow K, Palmqvist S, Stomrud E, Mattsson-Carlgren N, Hansson O (2024) Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases. Nat Commun 15:3676","journal-title":"Nat Commun"},{"key":"348_CR24","volume":"13","author":"A Keshavan","year":"2021","unstructured":"Keshavan A, Wellington H, Chen Z, Khatun A, Chapman M, Hart M, Cash DM, Coath W, Parker TD, Buchanan SM et al (2021) Concordance of CSF measures of Alzheimer\u2019s pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays. Alzheimers Dement Diagn Assess Dis Monit 13:e12131","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"},{"key":"348_CR25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-024-01650-1","volume":"17","author":"N Kimura","year":"2025","unstructured":"Kimura N, Sasaki K, Masuda T, Ataka T, Matsumoto M, Kitamura M, Nakamura Y, Matsubara E (2025) Machine learning models for dementia screening to classify brain amyloid positivity on positron emission tomography using blood markers and demographic characteristics: a retrospective observational study. Alzheimers Res Ther 17:1\u201314","journal-title":"Alzheimers Res Ther"},{"key":"348_CR26","volume":"15","author":"HS Kwon","year":"2023","unstructured":"Kwon HS, Lee E-H, Kim H-J, Park S-H, Park H-H, Jeong JH, Koh S-H, Choi SH, Lee J-H (2023) Predicting amyloid PET positivity using plasma p-tau181 and other blood-based biomarkers. Alzheimers Dement Diagn Assess Dis Monit 15:e12502","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"},{"key":"348_CR27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-024-00707-x","volume":"19","author":"J Lantero-Rodriguez","year":"2024","unstructured":"Lantero-Rodriguez J, Salvad\u00f3 G, Snellman A, Montoliu-Gaya L, Brum WS, Benedet AL, Mattsson-Carlgren N, Tideman P, Janelidze S, Palmqvist S et al (2024) Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer\u2019s Disease. Mol Neurodegener 19:19","journal-title":"Mol Neurodegener"},{"key":"348_CR28","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/ana.26891","volume":"95","author":"Y Li","year":"2024","unstructured":"Li Y, Yen D, Hendrix RD, Gordon BA, Dlamini S, Barth\u00e9lemy NR, Aschenbrenner AJ, Henson RL, Herries EM, Volluz K et al (2024) Timing of biomarker changes in sporadic Alzheimer\u2019s disease in estimated years from symptom onset. Ann Neurol 95:951\u2013965","journal-title":"Ann Neurol"},{"key":"348_CR29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1001\/jamaneurol.2016.6117","volume":"74","author":"N Mattsson","year":"2017","unstructured":"Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer\u2019s Disease Neuroimaging Initiative (2017) Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 74:557\u2013566","journal-title":"JAMA Neurol"},{"key":"348_CR30","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1001\/jamaneurol.2019.0765","volume":"76","author":"N Mattsson","year":"2019","unstructured":"Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K (2019a) Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol 76:791\u2013799","journal-title":"JAMA Neurol"},{"key":"348_CR31","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1001\/jamaneurol.2019.2214","volume":"76","author":"N Mattsson","year":"2019","unstructured":"Mattsson N, Palmqvist S, Stomrud E, Vogel J, Hansson O (2019b) Staging \u03b2-amyloid pathology with amyloid positron emission tomography. JAMA Neurol 76:1319\u20131329","journal-title":"JAMA Neurol"},{"key":"348_CR32","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aaz2387","volume":"6","author":"N Mattsson-Carlgren","year":"2020","unstructured":"Mattsson-Carlgren N, Andersson E, Janelidze S, Ossenkoppele R, Insel P, Strandberg O, Zetterberg H, Rosen HJ, Rabinovici G, Chai X et al (2020) A\u03b2 deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer\u2019s disease. Sci Adv 6:eaaz2387","journal-title":"Sci Adv"},{"key":"348_CR33","doi-asserted-by":"crossref","unstructured":"Mattsson-Carlgren N, Collij LE, Stomrud E, Pichet Binette A, Ossenkoppele R, Smith R, Karlsson L, Lantero-Rodriguez J, Snellman A, Strandberg O et al (2024) Plasma biomarker strategy for selecting patients with Alzheimer disease for antiamyloid immunotherapies. JAMA Neurol 81:69\u201378","DOI":"10.1001\/jamaneurol.2023.4596"},{"key":"348_CR34","doi-asserted-by":"crossref","first-page":"e1137","DOI":"10.1212\/WNL.0000000000200040","volume":"98","author":"N Mattsson-Carlgren","year":"2022","unstructured":"Mattsson-Carlgren N, Grinberg LT, Boxer A, Ossenkoppele R, Jonsson M, Seeley W, Ehrenberg A, Spina S, Janelidze S, Rojas-Martinex J et al (2022) Cerebrospinal fluid biomarkers in autopsy-confirmed Alzheimer disease and frontotemporal lobar degeneration. Neurology 98:e1137\u2013e1150","journal-title":"Neurology"},{"key":"348_CR35","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202114022","volume":"13","author":"N Mattsson-Carlgren","year":"2021","unstructured":"Mattsson-Carlgren N, Janelidze S, Bateman RJ, Smith R, Stomrud E, Serrano GE, Reiman EM, Palmqvist S, Dage JL, Beach TG et al (2021) Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med 13:e14022","journal-title":"EMBO Mol Med"},{"key":"348_CR36","first-page":"1797","volume":"28","author":"M Mil\u00e0-Alom\u00e0","year":"2022","unstructured":"Mil\u00e0-Alom\u00e0 M, Ashton NJ, Shekari M, Salvad\u00f3 G, Ortiz-Romero P, Montoliu-Gaya L, Benedet AL, Karikari TK, Lantero-Rodriguez J, Vanmechelen E et al (2022) Plasma p-tau231 and p-tau217 as state markers of amyloid-\u03b2 pathology in preclinical Alzheimer\u2019s disease. Nat Med 28:1797\u20131801","journal-title":"Nat Med"},{"key":"348_CR37","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13195-023-01302-w","volume":"15","author":"NS Mundada","year":"2023","unstructured":"Mundada NS, Rojas JC, Vandevrede L, Thijssen EH, Iaccarino L, Okoye OC, Shankar R, Soleimani-Meigooni DN, Lago AL, Miller BL et al (2023) Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment. Alzheimers Res Ther 15:157","journal-title":"Alzheimers Res Ther"},{"key":"348_CR38","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1038\/s41591-022-02049-x","volume":"28","author":"R Ossenkoppele","year":"2022","unstructured":"Ossenkoppele R, Pichet Binette A, Groot C, Smith R, Strandberg O, Palmqvist S, Stomrud E, Tideman P, Ohlsson T, J\u00f6gi J et al (2022) Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline. Nat Med 28:2381\u20132387","journal-title":"Nat Med"},{"key":"348_CR39","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jama.2020.12134","volume":"324","author":"S Palmqvist","year":"2020","unstructured":"Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, Su Y, Chen Y, Serrano GE, Leuzy A et al (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA 324:772\u2013781","journal-title":"JAMA"},{"key":"348_CR40","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1002\/alz.12751","volume":"19","author":"S Palmqvist","year":"2023","unstructured":"Palmqvist S, Stomrud E, Cullen N, Janelidze S, Manuilova E, Jethwa A, Bittner T, Eichenlaub U, Suridjan I, Kollmorgen G et al (2023) An accurate fully automated panel of plasma biomarkers for Alzheimer\u2019s disease. Alzheimers Dement 19:1204\u20131215","journal-title":"Alzheimers Dement"},{"key":"348_CR41","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/s41591-021-01348-z","volume":"27","author":"S Palmqvist","year":"2021","unstructured":"Palmqvist S, Tideman P, Cullen N, Zetterberg H, Blennow K, Dage JL, Stomrud E, Janelidze S, Mattsson-Carlgren N, Hansson O (2021) Prediction of future Alzheimer\u2019s disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med 27:1034\u20131042","journal-title":"Nat Med"},{"key":"348_CR42","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1001\/jamaneurol.2014.1358","volume":"71","author":"S Palmqvist","year":"2014","unstructured":"Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, Owenius R, H\u00e4gerstr\u00f6m D, Wollmer P, Minthon L et al (2014) Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid \u03b2-amyloid 42: a cross-validation study against amyloid positron emission tomography. JAMA Neurol 71:1282\u20131289","journal-title":"JAMA Neurol"},{"key":"348_CR43","unstructured":"Pelikan M, Goldberg DE, Cant\u00fa-Paz E (1999) BOA: the Bayesian optimization algorithm. In Proceedings of the 1st annual conference on genetic and evolutionary computation - Volume 1, 525\u2013532. Morgan Kaufmann Publishers Inc., San Francisco, CA, USA"},{"key":"348_CR44","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1093\/brain\/awab223","volume":"144","author":"JB Pereira","year":"2021","unstructured":"Pereira JB, Janelidze S, Smith R, Mattsson-Carlgren N, Palmqvist S, Teunissen CE, Zetterberg H, Stomrud E, Ashton NJ, Blennow K et al (2021) Plasma GFAP is an early marker of amyloid-\u03b2 but not tau pathology in Alzheimer\u2019s disease. Brain J Neurol 144:3505\u20133516","journal-title":"Brain J Neurol"},{"key":"348_CR45","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/s41591-023-02449-7","volume":"29","author":"C Quadalti","year":"2023","unstructured":"Quadalti C, Palmqvist S, Hall S, Rossi M, Mammana A, Janelidze S, Dellavalle S, Mattsson-Carlgren N, Baiardi S, Stomrud E et al (2023) Clinical effects of Lewy body pathology in cognitively impaired individuals. Nat Med 29:1964\u20131970","journal-title":"Nat Med"},{"key":"348_CR46","doi-asserted-by":"crossref","unstructured":"Rissman RA, Langford O, Raman R, Donohue MC, Abdel-Latif S, Meyer MR, Wente-Roth T, Kirmess KM, Ngolab J, Winston CN et al (2024) Plasma A\u03b242\/A\u03b240 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer\u2019s disease. Alzheimers Dement 20:1214\u20131224","DOI":"10.1002\/alz.13542"},{"key":"348_CR47","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202217123","volume":"15","author":"G Salvad\u00f3","year":"2023","unstructured":"Salvad\u00f3 G, Ossenkoppele R, Ashton NJ, Beach TG, Serrano GE, Reiman EM, Zetterberg H, Mattsson-Carlgren N, Janelidze S, Blennow K et al (2023) Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO Mol Med 15:e17123","journal-title":"EMBO Mol Med"},{"key":"348_CR48","doi-asserted-by":"crossref","first-page":"e1647","DOI":"10.1212\/WNL.0000000000008081","volume":"93","author":"SE Schindler","year":"2019","unstructured":"Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C et al (2019) High-precision plasma \u03b2-amyloid 42\/40 predicts current and future brain amyloidosis. Neurology 93:e1647\u2013e1659","journal-title":"Neurology"},{"key":"348_CR49","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/j.jalz.2018.07.220","volume":"14","author":"LM Shaw","year":"2018","unstructured":"Shaw LM, Arias J, Blennow K, Galasko D, Molinuevo JL, Salloway S, Schindler S, Carrillo MC, Hendrix JA, Ross A et al (2018) Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer\u2019s disease. Alzheimers Dement 14:1505\u20131521","journal-title":"Alzheimers Dement"},{"key":"348_CR50","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","volume":"330","author":"JR Sims","year":"2023","unstructured":"Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES et al (2023) Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330:512\u2013527","journal-title":"JAMA"},{"key":"348_CR51","unstructured":"Snoek J, Larochelle H, Adams RP (2012) Practical Bayesian optimization of machine learning algorithms. In: Advances in neural information processing systems. Curran Associates, Inc."},{"key":"348_CR52","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S et al (2023) Lecanemab in early Alzheimer\u2019s disease. N Engl J Med 388:9\u201321","journal-title":"N Engl J Med"},{"key":"348_CR53","volume":"15","author":"JK Wisch","year":"2023","unstructured":"Wisch JK, Gordon BA, Boerwinkle AH, Luckett PH, Bollinger JG, Ovod V, Li Y, Henson RL, West T, Meyer MR et al (2023) Predicting continuous amyloid PET values with CSF and plasma A\u03b242\/A\u03b240. Alzheimers Dement Diagn Assess Dis Monit 15:e12405","journal-title":"Alzheimers Dement Diagn Assess Dis Monit"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44321-025-00348-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/s44321-025-00348-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44321-025-00348-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:28:07Z","timestamp":1786962487000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/s44321-025-00348-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,15]]}},"alternative-id":["348"],"URL":"https:\/\/doi.org\/10.1038\/s44321-025-00348-7","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"assertion":[{"value":"18 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"NMC has received consulting\/speaker fees from BioArctic, Biogen, Eli Lilly, Merck, Novo Nordisk, and Owkin. KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. SP has acquired research support (for the institution) from ki elements\/ADDF and Avid. In the past 2 years, he has received consultancy\/speaker fees from Bioartic, Biogen, Esai, Eli Lilly, and Roche. SES has served on scientific advisory boards on biomarker testing and clinical treatment pathways for Eisai and Novo Nordisk, and has received speaking fees from Eli Lilly. OH is an employee of Lund University and Eli Lilly.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"9"}}