{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:24:22Z","timestamp":1792679062473,"version":"4.5.0"},"reference-count":54,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec id=\"ab-noi230014-4\"><jats:title>Importance<\/jats:title><jats:p>Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)\u2013associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230014-5\"><jats:title>Objective<\/jats:title><jats:p>To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230014-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n\u2009=\u2009113), PSP-RS (n\u2009=\u2009121), and nfvPPA (n\u2009=\u200939) were included; other diagnoses were excluded due to rarity (n\u2009=\u200929). Individuals with PET-confirmed AD (n\u2009=\u200954) and PET-negative cognitively normal control individuals (n\u2009=\u200959) were evaluated at University of California San Francisco. Operators were blinded to the cohort.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230014-7\"><jats:title>Main Outcome and Measures<\/jats:title><jats:p>Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-\u03b2 (A\u03b2) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling.<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230014-8\"><jats:title>Results<\/jats:title><jats:p>Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive A\u03b2 PET results (mean [SD], 0.57 [0.43] pg\/mL) or FTP PET (mean [SD], 0.75 [0.30] pg\/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for A\u03b2 PET of 0.87 (95% CI, 0.76-0.98; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) and FTP PET of 0.93 (95% CI, 0.83-1.00; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). At baseline, individuals with CBS-AD (n\u2009=\u200912), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg\/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n\u2009=\u200939), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points\/year; <jats:italic>P<\/jats:italic>\u2009=\u2009.005).<\/jats:p><\/jats:sec><jats:sec id=\"ab-noi230014-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying A\u03b2 or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.0488","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T15:05:56Z","timestamp":1680534356000},"page":"495","source":"Crossref","is-referenced-by-count":45,"title":["Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome"],"prefix":"10.1001","volume":"80","author":[{"given":"Lawren","family":"VandeVrede","sequence":"first","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California San Francisco Weill Institute for Neurosciences, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory 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