{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:14:33Z","timestamp":1792800873133,"version":"4.5.0"},"reference-count":53,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:sec id=\"ab-noi220081-4\"><jats:title>Importance<\/jats:title><jats:p>The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-\u03b2 plaques and tau neurofibrillary tangles.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-5\"><jats:title>Objective<\/jats:title><jats:p>To determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral \u03b2-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET).<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau<jats:sub>181<\/jats:sub>, p-tau<jats:sub>217<\/jats:sub>, p-tau<jats:sub>231<\/jats:sub>, p-tau<jats:sub>235<\/jats:sub>), [<jats:sup>18<\/jats:sup>F]AZD4694 amyloid PET, and [<jats:sup>18<\/jats:sup>F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau<jats:sub>181<\/jats:sub>, p-tau<jats:sub>217<\/jats:sub>, p-tau<jats:sub>231<\/jats:sub>), [<jats:sup>18<\/jats:sup>F]AZD4694 amyloid PET, and [<jats:sup>18<\/jats:sup>F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau<jats:sub>181<\/jats:sub>, [<jats:sup>18<\/jats:sup>F]florbetapir PET, and [<jats:sup>18<\/jats:sup>F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging\/PET safety contraindications. No participants who met eligibility criteria were excluded.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-7\"><jats:title>Exposures<\/jats:title><jats:p>Amyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Associations between p-tau biomarkers with amyloid PET and tau PET.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-9\"><jats:title>Results<\/jats:title><jats:p>A total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau<jats:sub>181<\/jats:sub> difference, 13%; 95% CI, 3%-22%; <jats:italic>P<\/jats:italic>\u2009=\u2009.006; p-tau<jats:sub>217<\/jats:sub> difference, 11%; 95% CI, 3%-20%; <jats:italic>P<\/jats:italic>\u2009=\u2009.003; p-tau<jats:sub>231<\/jats:sub> difference, 15%; 95% CI, 5%-22%; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001; p-tau<jats:sub>235<\/jats:sub> difference, 9%; 95% CI, 1%-19%; <jats:italic>P<\/jats:italic>\u2009=\u2009.02) . These results were replicated with plasma p-tau<jats:sub>181<\/jats:sub> (difference, 11%; 95% CI, 1%-22%; <jats:italic>P<\/jats:italic>\u2009=\u2009.02), p-tau<jats:sub>217<\/jats:sub> (difference, 9%; 95% CI, 1%-19%; <jats:italic>P<\/jats:italic>\u2009=\u2009.02), p-tau<jats:sub>231<\/jats:sub> (difference, 13%; 95% CI, 3%-24%; <jats:italic>P<\/jats:italic>\u2009=\u2009.009), and CSF p-tau<jats:sub>181<\/jats:sub> (difference, 9%; 95% CI, 1%-21%; <jats:italic>P<\/jats:italic>\u2009=\u2009.02) in independent cohorts.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi220081-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-\u03b2 accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid\/tau\/neurodegeneration, or A\/T\/(N), framework.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2022.4485","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T16:00:52Z","timestamp":1670860852000},"page":"188","source":"Crossref","is-referenced-by-count":284,"title":["Association of Phosphorylated Tau Biomarkers With Amyloid Positron Emission Tomography vs Tau Positron Emission Tomography"],"prefix":"10.1001","volume":"80","author":[{"given":"Joseph","family":"Therriault","sequence":"first","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, Canada"},{"name":"Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Vermeiren","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Montreal, Quebec, 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