{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:24:13Z","timestamp":1794007453938,"version":"4.8.0"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"\n Importance<\/jats:title>\n Blood-based tests for brain amyloid-\u03b2 (A\u03b2) pathology are needed for widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening and monitoring of treatment responses in clinical trials.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare the performance of plasma A\u03b242\/40 measured using 8 different A\u03b2 assays when detecting abnormal brain A\u03b2 status in patients with early AD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This study included 182 cognitively unimpaired participants and 104 patients with mild cognitive impairment from the BioFINDER cohort who were enrolled at 3 different hospitals in Sweden and underwent A\u03b2 positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) and plasma collection from 2010 to 2014. Plasma A\u03b242\/40 was measured using an immunoprecipitation-coupled mass spectrometry developed at Washington University (IP-MS-WashU), antibody-free liquid chromatography MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma A\u03b242\/40 was also measured using an IP-MS\u2013based method from Shimadzu in 200 participants (IP-MS-Shim) and an IP-MS\u2013based method from the University of Gothenburg (IP-MS-UGOT) and another immunoassay from Quanterix (IA-Quan) among 227 participants. For validation, 122 participants (51 cognitively normal, 51 with mild cognitive impairment, and 20 with AD dementia) were included from the Alzheimer Disease Neuroimaging Initiative who underwent A\u03b2-PET and plasma A\u03b2 assessments using IP-MS-WashU, IP-MS-Shim, IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Discriminative accuracy of plasma A\u03b242\/40 quantified using 8 different assays for abnormal CSF A\u03b242\/40 and A\u03b2-PET status.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 408 participants were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF A\u03b242\/40 in the whole cohort, plasma IP-MS-WashU A\u03b242\/40 showed significantly higher accuracy (area under the receiver operating characteristic curve [AUC], 0.86; 95% CI, 0.81-0.90) than LC-MS-Arc A\u03b242\/40, IA-Elc A\u03b242\/40, IA-EI A\u03b242\/40, and IA-N4PE A\u03b242\/40 (AUC range, 0.69-0.78;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.05). Plasma IP-MS-WashU A\u03b242\/40 performed significantly better than IP-MS-UGOT A\u03b242\/40 and IA-Quan A\u03b242\/40 (AUC, 0.84 vs 0.68 and 0.64, respectively;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), while there was no difference in the AUCs between IP-MS-WashU A\u03b242\/40 and IP-MS-Shim A\u03b242\/40 (0.87 vs 0.83;\n P<\/jats:italic>\n \u2009=\u2009.16) in the 2 subcohorts where these biomarkers were available. The results were similar when using A\u03b2-PET as outcome. Plasma IPMS-WashU A\u03b242\/40 and IPMS-Shim A\u03b242\/40 showed highest coefficients for correlations with CSF A\u03b242\/40 (\n r<\/jats:italic>\n range, 0.56-0.65). The BioFINDER results were replicated in the Alzheimer Disease Neuroimaging Initiative cohort (mean [SD] age, 72.4 [5.4] years; 43.4% women), where the IP-MS-WashU assay performed significantly better than the IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays but not the IP-MS-Shim assay.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The results from 2 independent cohorts indicate that certain MS-based methods performed better than most of the immunoassays for plasma A\u03b242\/40 when detecting brain A\u03b2 pathology.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2021.3180","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T11:35:24Z","timestamp":1632137724000},"page":"1375","source":"Crossref","is-referenced-by-count":490,"title":["Head-to-Head Comparison of 8 Plasma Amyloid-\u03b2 42\/40 Assays in Alzheimer Disease"],"prefix":"10.1001","volume":"78","author":[{"given":"Shorena","family":"Janelidze","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience & Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, University College London Institute of Neurology, London, United Kingdom"},{"name":"United Kingdom Dementia Research Institute at University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Allu\u00e9","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Araclon Biotech, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Sarasa","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Araclon Biotech, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Eichenlaub","sequence":"additional","affiliation":[{"name":"Roche Diagnostics, Penzberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bittner","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy","family":"Ovod","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M. W.","family":"Verberk","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Toba","sequence":"additional","affiliation":[{"name":"National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"},{"name":"Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, Missouri"}],"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 & 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, Lund, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"noi210057r1","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","article-title":"Biomarkers for neurodegenerative diseases.","volume":"27","author":"Hansson","year":"2021","journal-title":"Nat Med"},{"issue":"7","key":"noi210057r2","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S1474-4422(16)00070-3","article-title":"CSF and blood biomarkers for the diagnosis of Alzheimer\u2019s disease: a systematic review and meta-analysis.","volume":"15","author":"Olsson","year":"2016","journal-title":"Lancet Neurol"},{"key":"noi210057r3","doi-asserted-by":"publisher","first-page":"26801","DOI":"10.1038\/srep26801","article-title":"Plasma \u00df-amyloid in Alzheimer\u2019s disease and vascular disease.","volume":"6","author":"Janelidze","year":"2016","journal-title":"Sci Rep"},{"issue":"7691","key":"noi210057r4","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature25456","article-title":"High performance plasma amyloid-\u00df biomarkers for Alzheimer\u2019s disease.","volume":"554","author":"Nakamura","year":"2018","journal-title":"Nature"},{"issue":"8","key":"noi210057r5","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.jalz.2017.06.2266","article-title":"Amyloid \u00df concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis.","volume":"13","author":"Ovod","year":"2017","journal-title":"Alzheimers Dement"},{"issue":"17","key":"noi210057r6","doi-asserted-by":"publisher","first-page":"e1647","DOI":"10.1212\/WNL.0000000000008081","article-title":"High-precision plasma \u00df-amyloid 42\/40 predicts current and future brain amyloidosis.","volume":"93","author":"Schindler","year":"2019","journal-title":"Neurology"},{"issue":"9","key":"noi210057r7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1001\/jamaneurol.2019.1632","article-title":"Performance of fully automated plasma assays as screening tests for Alzheimer disease-related \u00df-amyloid status.","volume":"76","author":"Palmqvist","year":"2019","journal-title":"JAMA Neurol"},{"issue":"5","key":"noi210057r8","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/ana.v84.5","article-title":"Plasma amyloid as prescreener for the earliest Alzheimer pathological changes.","volume":"84","author":"Verberk","year":"2018","journal-title":"Ann Neurol"},{"issue":"8","key":"noi210057r10","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders.","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA"},{"issue":"1","key":"noi210057r11","doi-asserted-by":"publisher","first-page":"9736","DOI":"10.1038\/s41598-021-89004-x","article-title":"Highly specific and ultrasensitive plasma test detects Abeta(1-42) and Abeta(1-40) in Alzheimer\u2019s disease.","volume":"11","author":"Thijssen","year":"2021","journal-title":"Sci Rep"},{"key":"noi210057r12","doi-asserted-by":"publisher","DOI":"10.1002\/alz.v18.2","article-title":"Detecting amyloid positivity in early Alzheimer\u2019s disease using combinations of plasma A\u00df42\/40 and p-tau.","author":"Janelidze","journal-title":"Alzheimers Dement"},{"issue":"10","key":"noi210057r13","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1001\/jamaneurol.2014.1358","article-title":"Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid \u00df-amyloid 42: a cross-validation study against amyloid positron emission tomography.","volume":"71","author":"Palmqvist","year":"2014","journal-title":"JAMA Neurol"},{"issue":"6","key":"noi210057r14","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/ana.23908","article-title":"Comparing positron emission tomography imaging and cerebrospinal fluid measurements of \u00df-amyloid.","volume":"74","author":"Landau","year":"2013","journal-title":"Ann Neurol"},{"issue":"4","key":"noi210057r15","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1002\/ana.23650","article-title":"Amyloid deposition, hypometabolism, and longitudinal cognitive decline.","volume":"72","author":"Landau","year":"2012","journal-title":"Ann Neurol"},{"issue":"1","key":"noi210057r16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13195-020-00585-7","article-title":"Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases.","volume":"12","author":"Minta","year":"2020","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"noi210057r17","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1001\/jamaneurol.2020.4201","article-title":"Associations of plasma phospho-tau217 levels with tau positron emission tomography in early Alzheimer disease.","volume":"78","author":"Janelidze","year":"2021","journal-title":"JAMA Neurol"},{"issue":"2","key":"noi210057r18","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1093\/clinchem\/hvz022","article-title":"Protein biomarker quantification by immunoaffinity liquid chromatography-tandem mass spectrometry: current state and future vision.","volume":"66","author":"Neubert","year":"2020","journal-title":"Clin Chem"},{"issue":"11","key":"noi210057r19","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1016\/j.jalz.2018.01.010","article-title":"CSF biomarkers of Alzheimer\u2019s disease concord with amyloid-\u00df PET and predict clinical progression: a study of fully automated immunoassays in BioFINDER and ADNI cohorts.","volume":"14","author":"Hansson","year":"2018","journal-title":"Alzheimers Dement"},{"key":"noi210057r9","unstructured":"ADNI. Alzheimer\u2019s Disease Neuroimaging Initiative. Accessed June 25, 2021. http:\/\/adni.loni.usc.edu\/"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2784411\/jamaneurology_janelidze_2021_oi_210057_1673639379.56508.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T11:14:41Z","timestamp":1673954081000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2784411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2021.3180","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}