{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:17:09Z","timestamp":1792891029617,"version":"4.5.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:sec id=\"ab-noi230088-4\"><jats:title>Importance<\/jats:title><jats:p>Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid \u03b2 (A\u03b2)\u2013positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-5\"><jats:title>Objective<\/jats:title><jats:p>To evaluate plasma biomarkers for identifying A\u03b2 positivity and stage of tau accumulation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>The cohort study (BioFINDER-2) was a prospective memory-clinic and population-based study. Participants with cognitive concerns were recruited from 2017 to 2022 and divided into a training set (80% of the data) and test set (20%).<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-7\"><jats:title>Exposure<\/jats:title><jats:p>Baseline values for plasma phosphorylated tau 181 (p-tau181), p-tau217, p-tau231, N-terminal tau, glial fibrillary acidic protein, and neurofilament light chain.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Performance to classify participants by A\u03b2 status (defined by A\u03b2-PET or CSF A\u03b242\/40) and tau status (tau PET). Number of hypothetically saved PET scans in a plasma biomarker\u2013guided workflow.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-9\"><jats:title>Results<\/jats:title><jats:p>Of a total 912 participants, there were 499 males (54.7%) and 413 females (45.3%), and the mean (SD) age was 71.1 (8.49) years. Among the biomarkers, plasma p-tau217 was most strongly associated with A\u03b2 positivity (test-set area under the receiver operating characteristic curve [AUC]\u2009=\u20090.94; 95% CI, 0.90-0.97). A 2\u2013cut-point procedure was evaluated, where only participants with ambiguous plasma p-tau217 values (17.1% of the participants in the test set) underwent CSF or PET to assign definitive A\u03b2 status. This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95). Next, plasma biomarkers were used to differentiate low-intermediate vs high tau-PET load among A\u03b2-positive participants. Plasma p-tau217 again performed best, with the test AUC\u2009=\u20090.92 (95% CI, 0.86-0.97), without significant improvement when adding any of the other plasma biomarkers. At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among A\u03b2-positive participants. The results were validated in an independent cohort (n\u2009=\u2009118).<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230088-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This study found that algorithms using plasma p-tau217 can accurately identify most A\u03b2-positive individuals, including those likely to have a high tau load who would require confirmatory tau-PET imaging. Plasma p-tau217 measurements may substantially reduce the number of invasive and costly confirmatory tests required to identify individuals who would likely benefit from antiamyloid therapies.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.4596","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T16:01:20Z","timestamp":1701705680000},"page":"69","source":"Crossref","is-referenced-by-count":148,"title":["Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies"],"prefix":"10.1001","volume":"81","author":[{"given":"Niklas","family":"Mattsson-Carlgren","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"},{"name":"Department of Neurology, Sk\u00e5ne University Hospital, Lund University, Lund, Sweden"},{"name":"Wallenberg Center for Molecular Medicine, Lund University, Lund, 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