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<jats:p>Phosphorylated tau 217 (p-tau217) has emerged as a leading blood-based biomarker for Alzheimer disease (AD). While typically measured in plasma, serum is a widely used matrix in clinical laboratories, yet few p-tau217 assays have been validated for serum. Evaluating serum p-tau217 performance is essential for expanding its use in clinical and research settings, particularly for cohorts with only serum samples available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We quantified p-tau217 in plasma and serum from individuals within the AD continuum (n = 100; mean age 72.5 \u00b1 5.0 years; 54% female) using 6 assays across 4 platforms. Spearman correlation, Passing\u2013Bablok regression, and receiver operating characteristics analysis were used to assess intermatrix agreement and diagnostic performance. Specific validation parameters (e.g., precision, parallelism, dilution linearity, stability) were evaluated in both matrices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High correlations between plasma and serum were observed for most assays (\u03c1 &amp;gt; 0.8), though plasma often yielded higher concentrations. Notably, the Lumipulse assay showed near-perfect correlation (\u03c1 = 0.98) and minimal bias. Fold changes in p-tau217 levels across the AD continuum were comparable between matrices, though cutoffs for detecting AD pathology differed. Applying plasma-derived cutoffs to serum resulted in misclassification rates ranging from 16% to 47%, except for Lumipulse (10% in serum vs 5% in plasma). Not all assays performed equally in serum, as reflected in validation metrics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum p-tau217, across multiple platforms, shows strong correlations with plasma p-tau217 and reflected comparable patterns across the AD continuum. However, absolute concentrations differed for most assays, thus requiring differing disease specific cutoffs. Most of the evaluated platforms demonstrated reliable quantification of p-tau217 in serum, yielding satisfactory validation performance. These findings support serum as a viable alternative to plasma for p-tau217 quantification in both research and clinical settings, provided matrix-specific validation is ensured.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaf162","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T16:58:37Z","timestamp":1763053117000},"page":"303-315","source":"Crossref","is-referenced-by-count":10,"title":["Diagnostic Value of Serum p-tau217 in Alzheimer Disease: Equal to Plasma in Levels and Clinical Utility?"],"prefix":"10.1093","volume":"72","author":[{"given":"Andrea L","family":"Benedet","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-3226","authenticated-orcid":false,"given":"Burak","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kubra","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and 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,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4481-508X","authenticated-orcid":false,"given":"Hlin","family":"Kvartsberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["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 ,","place":["Sweden"]}],"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 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , Gothenburg ,","place":["Sweden"]},{"name":"Paris Brain Institute, ICM, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Sorbonne University , Paris ,","place":["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 USTC , Hefei ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , Gothenburg ,","place":["Sweden"]},{"name":"School of Medicine and Public Health, Wisconsin Alzheimer\u2019s Institute, University of Wisconsin , Madison, WI ,","place":["United States"]},{"name":"Department of Neurodegenerative Disease, Institute of Neurology, University College London , London ,","place":["United Kingdom"]},{"name":"UK Dementia Research Institute, University College London , London ,","place":["United Kingdom"]},{"name":"Hong Kong Center for Neurodegenerative Diseases , Hong Kong 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