{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T11:27:30Z","timestamp":1794569250062,"version":"4.9.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2023,4]]},"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n \n Further evidence is needed to support the use of plasma amyloid \u03b2 (A\u03b2) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n for amyloid positivity prescreening.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n evaluated the actionability of plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n , and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Elecsys plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n could potentially rule out amyloid pathology in populations with low\u2010to\u2010moderate amyloid positivity prevalence. However, simulations showed small measurement or pre\u2010analytical errors in A\u03b2\n 42<\/jats:sub>\n and\/or A\u03b2\n 40<\/jats:sub>\n cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n Implementing plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n for routine clinical use may pose significant challenges, with misclassification risks.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n Plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n ruled out amyloid PET positivity in a setting of low amyloid\u2010positive prevalence.\n <\/jats:p>\n <\/jats:list-item>\n \n Including (pre\u2010) analytical errors or measurement biases caused misclassifications.<\/jats:p>\n <\/jats:list-item>\n \n \n Plasma A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n had a low inherent dynamic range, independent of analytical method.\n <\/jats:p>\n <\/jats:list-item>\n \n Other blood biomarkers may be easier to implement as robust prescreening tools.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.12801","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T14:42:58Z","timestamp":1663944178000},"page":"1393-1402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Clinical performance and robustness evaluation of plasma amyloid\u2010\u03b2\n 42\/40<\/sub>\n prescreening"],"prefix":"10.1002","volume":"19","author":[{"given":"Christina","family":"Rabe","sequence":"first","affiliation":[{"name":"Genentech, Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bittner","sequence":"additional","affiliation":[{"name":"Genentech, Inc. South San Francisco California USA"},{"name":"F. Hoffmann\u2010La Roche Ltd Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Jethwa","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Suridjan","sequence":"additional","affiliation":[{"name":"Roche Diagnostics International Ltd Rotkreuz Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Manuilova","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Friesenhahn","sequence":"additional","affiliation":[{"name":"Genentech, Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit Department of Clinical Sciences Malm\u00f6 Lund University Malm\u00f6 Sweden"},{"name":"Memory Clinic Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology London UK"},{"name":"UK Dementia Research Institute at UCL London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit Department of Clinical Sciences Malm\u00f6 Lund University Malm\u00f6 Sweden"},{"name":"Memory Clinic Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative and the Swedish BioFINDER study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12328"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01124-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01382-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-017-0073-9"},{"key":"e_1_2_8_6_1","article-title":"Expected wait times for access to a disease\u2010modifying Alzheimer's treatment in the United States","author":"Mattke S","year":"2021","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_7_1","article-title":"Blood\u2010based biomarkers for Alzheimer's pathology and the diagnostic process for a disease\u2010modifying treatment: Projecting the impact on the cost and wait times","volume":"12","author":"Mattke S","journal-title":"Alzheimers Dement (Amst)"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25456"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.06.2266"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.1632"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3180"},{"key":"e_1_2_8_12_1","volume-title":"The Statistical Evaluation of Medical Tests for Classification and Prediction","author":"Pepe M.","year":"2004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm305"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2018.300954"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00942-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2019.02.002"},{"key":"e_1_2_8_17_1","unstructured":"VerberkIMW MisdorpEO KoelewijnJ et\u00a0al.Characterization of pre\u2010analytical sample handling effects on a panel of Alzheimer's disease\u2013related blood\u2010based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group. Alzheimers Dement;epub ahead of print."},{"key":"e_1_2_8_18_1","first-page":"819","article-title":"Analytical performance, reference values and decision limits. A need to differentiate between reference intervals and decision limits and to define analytical quality specifications","volume":"50","author":"Petersen PH","year":"2011","journal-title":"Clin Chem Lab Med"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191191"},{"key":"e_1_2_8_20_1","unstructured":"Foundation for the National Institutes ofHealth(FNIH).Biomarkers consortium \u2010 plasma A\u03b2 as a predictor of amyloid positivity in Alzheimer's Disease. Accessed April 4 2022.https:\/\/fnih.org\/our\u2010programs\/biomarkers\u2010consortium\/programs\/plasma\u2010abeta"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.010"},{"key":"e_1_2_8_22_1","unstructured":"Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI FNIH method sheet. Accessed April 4 2022.http:\/\/adni.loni.usc.edu\/data\u2010samples\/access\u2010data\/"},{"key":"e_1_2_8_23_1","unstructured":"FrankHarrell.Clinicians' misunderstanding of probabilities makes them like backwards probabilities such as sensitivity specificity and type I error. Accessed April 4 2022.https:\/\/www.fharrell.com\/post\/backwards\u2010probs\/"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2015-0710"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.0387"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.09.014"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0079-7"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00451-6"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12134"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-01137-1"}],"container-title":["Alzheimer's & Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12801","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12801","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:01:00Z","timestamp":1759957260000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/alz.12801"],"URL":"https:\/\/doi.org\/10.1002\/alz.12801","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]},"assertion":[{"value":"2022-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}