{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:49:09Z","timestamp":1793828949260,"version":"4.6.1"},"reference-count":50,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec id=\"ab-noi250060-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid \u03b2 (A\u03b2) pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying A\u03b2 status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (A\u03b2 positron emission tomography [PET] or cerebrospinal fluid [CSF]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET A\u03b2 biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n\u2009=\u2009964).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>Plasma p-tau217 levels measured by immunoassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-8\">\n                    <jats:title>Main Outcome and Measures<\/jats:title>\n                    <jats:p>A\u03b2 status, determined by CSF or A\u03b2 PET biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were A\u03b2 positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 A\u03b2-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) and true A\u03b2-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi250060-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The findings highlight the potential of plasma p-tau217 as a stand-alone test\u2014or when used in a sequential 2-step approach alongside PET or CSF testing\u2014as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.3217","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T15:00:23Z","timestamp":1757948423000},"page":"1122","source":"Crossref","is-referenced-by-count":89,"title":["Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease"],"prefix":"10.1001","volume":"82","author":[{"given":"Gemma","family":"Salvad\u00f3","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"},{"name":"Barcelona\u00dfeta Brain Research Center, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Bali","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Ordu\u00f1a","family":"Dolado","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Therriault","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McConnell Brain Imaging Centre, The McGill University Research Centre for Studies in Aging, Montr\u00e9al, Quebec, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner S.","family":"Brum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Pichet Binette","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden"}],"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, Lund, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Mattsson-Carlgren","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"},{"name":"Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Palmqvist","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"}]},{"given":"Emma M.","family":"Coomans","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Brain Imaging, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"},{"name":"Epidemiology and Data Science, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McConnell Brain Imaging Centre, The McGill University Research Centre for Studies in Aging, Montr\u00e9al, Quebec, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie L. S.","family":"Benzinger","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine in St Louis, St Louis, Missouri"},{"name":"Knight Alzheimer Disease Research Center, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Domingo","family":"Gispert","sequence":"additional","affiliation":[{"name":"Barcelona\u00dfeta Brain Research Center, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Bioingenier\u00eda, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Universitat Pompeu Fabra, Barcelona, Spain"},{"name":"Hospital del Mar Medical Research Institute, Barcelona, Spain"},{"name":"Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain"}],"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, Gothenburg, Sweden"},{"name":"Paris Brain Institute, ICM, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University, Paris, France"},{"name":"Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of the University of Science and Technology of China, Hefei, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Dor\u00e9","sequence":"additional","affiliation":[{"name":"Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia"},{"name":"The Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Feizpour","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia"},{"name":"Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Victoria, Australia"},{"name":"Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia"},{"name":"Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Victoria, Australia"},{"name":"Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, 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