{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:20:05Z","timestamp":1790400005365,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201022\u2010973496"],"award-info":[{"award-number":["AARG\u201022\u2010973496"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007453","name":"Stiftung VERUM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>With the advent of disease\u2010modifying therapies, accurate assessment of biomarkers indicating the presence of disease\u2010associated amyloid beta (A\u03b2) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated A\u03b2 levels in cerebrospinal fluid (A\u03b2 CSF) and A\u03b2 levels in positron emission tomography (A\u03b2 PET) biomarkers in a real\u2010world memory\u2010clinic setting to develop an efficient algorithm for clinical use.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients were evaluated for AD\u2010related A\u03b2 pathology from two independent cohorts (Ludwig Maximilian University [LMU], <jats:italic>n<\/jats:italic>\u00a0=\u00a0402, and Medical University of Vienna [MUV], <jats:italic>n<\/jats:italic>\u00a0=\u00a0144). Optimal thresholds of CSF biomarkers were deduced from receiver operating characteristic curves and validated against A\u03b2 PET positivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In both cohorts, a CSF A\u03b242\/40 ratio\u00a0\u2265\u00a07.1% was associated with a low risk of a positive A\u03b2 PET scan (negative predictive value: 94.3%). Implementing two cutoffs revealed 14% to 16% of\u00a0patients with intermediate results (CSF A\u03b242\/40 ratio: 5.5%\u20137.1%), which had a strong benefit from A\u03b2 PET imaging (44%\u201352% A\u03b2 PET positivity).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>A two\u2010cutoff approach for CSF A\u03b242\/40 including A\u03b2 PET imaging at intermediate results provides an effective assessment of A\u03b2 pathology in real\u2010world settings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) amyloid beta (A\u03b2) biomarkers for Alzheimer's disease in real\u2010world cohorts.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A CSF A\u03b2 42\/40 ratio between 5.5% and 7.1% defines patients at borderline levels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Patients at borderline levels strongly benefit from additional A\u03b2 PET imaging.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two\u2010cutoff CSF A\u03b2 42\/40 and PET will allow effective treatment stratification.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70031","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T07:00:17Z","timestamp":1732258817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A\u03b2 status assessment in a hypothetical scenario prior to treatment with disease\u2010modifying therapies: Evidence from 10\u2010year real\u2010world experience at university memory clinics"],"prefix":"10.1002","volume":"16","author":[{"given":"Matthias","family":"Brendel","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine LMU University Hospital, LMU Munich Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tandis","family":"Parvizi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU University Hospital, LMU Munich Munich Germany"},{"name":"Department of Neurology Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gn\u00f6rich","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof Elias","family":"Topfstedt","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD) LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Buerger","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Institute for Stroke and Dementia Research (ISD) LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Janowitz","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD) LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris\u2010Stephan","family":"Rauchmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Perneczky","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"},{"name":"Ageing Epidemiology (AGE) Research Unit, School of Public Health Imperial College London London UK"},{"name":"Sheffield Institute for Translational Neuroscience (SITraN) University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Mehrens","sequence":"additional","affiliation":[{"name":"Department of Radiology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang G.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Department of Radiology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kusche\u2010Palenga","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes Bernadette","family":"Kling","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Buchal","sequence":"additional","affiliation":[{"name":"Department of Radiology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabet","family":"Nestorova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Silvaieh","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Wurm","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Traub\u2010Weidinger","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna Vienna Austria"},{"name":"Department of Diagnostic and Therapeutic Nuclear Medicine Klinik Donaustadt Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Klotz","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"},{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnther","family":"Regelsberger","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"},{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital Bern University Hospital, University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Drzezga","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Faculty of Medicine and University Hospital Cologne Cologne Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn Germany"},{"name":"Institute of Neuroscience and Medicine (INM\u20102), Molecular Organization of the Brain Forschungszentrum J\u00fclich J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"},{"name":"Department of Neurology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"St\u00f6gmann","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"},{"name":"Institute for Stroke and Dementia Research (ISD) LMU University Hospital, LMU Munich Munich Germany"},{"name":"The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, M\u00f6lndal and Gothenburg University of Gothenburg M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"},{"name":"Department of Neurology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00447-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00595-5"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1358"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001991"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.81"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010739"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-132561"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu367"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0532-x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr179"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821103e6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827f0fd1"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000034"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610214002245"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.12.009"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40211-015-0141-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00115-006-2098-7"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.4.609"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1159"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12316"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01036-3"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506120009146438"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.2008"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.02.004"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02869-z"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00471-5"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00403-3"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.07.003"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww015"},{"issue":"1","key":"e_1_2_12_35_1","article-title":"Comparing CSF amyloid\u2010beta biomarker ratios for two automated immunoassays, Elecsys and Lumipulse, with amyloid PET status","volume":"13","author":"Willemse EAJ","year":"2021","journal-title":"Alzheimers Dement"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.010"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.013"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0485-0"},{"issue":"3","key":"e_1_2_12_39_1","first-page":"2","article-title":"Assessing the preparedness of the health care system infrastructure in six European countries for an Alzheimer's treatment","volume":"8","author":"Hlavka JP","year":"2019","journal-title":"Rand Heal Q"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00066-1"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-011146"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.06.006"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.893"},{"issue":"3","key":"e_1_2_12_44_1","article-title":"Harmonization and standardization of biofluid\u2010based biomarker measurements for AT(N) classification in Alzheimer's disease","volume":"15","author":"Giangrande C","year":"2023","journal-title":"Alzheimers Dement"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-016-3591-2"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2022.09.008"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0315"}],"container-title":["Alzheimer's &amp; Dementia: Diagnosis, Assessment &amp; Disease Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dad2.70031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T18:45:58Z","timestamp":1760381158000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/dad2.70031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/dad2.70031"],"URL":"https:\/\/doi.org\/10.1002\/dad2.70031","archive":["Portico"],"relation":{},"ISSN":["2352-8729","2352-8729"],"issn-type":[{"value":"2352-8729","type":"print"},{"value":"2352-8729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70031"}}