{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:02:46Z","timestamp":1784887366611,"version":"3.55.0"},"posted":{"date-parts":[[2026,3,27]]},"group-title":"Neurology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Objectives<\/jats:title>\n                  <jats:p>While plasma phosphorylated tau-217 (pTau217) detects co-occurring Alzheimer\u2019s disease (AD) neuropathologic change in Lewy body disease (LBD), relationships with long-term clinical outcomes remain unclear. Our aim was to evaluate plasma pTau217 as a prognostic, risk-stratification, and monitoring biomarker of cognitive and functional decline in LBD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This prospective longitudinal study included Stanford Alzheimer\u2019s Disease Research Center participants enrolled from 2015-2023 with plasma pTau217 data and clinical diagnoses of LBD spectrum, AD spectrum, or healthy control (HC). To evaluate prognostic and monitoring utility, respectively, linear mixed-effect models tested whether baseline level and longitudinal change (2-5 years) in plasma pTau217 were associated with longitudinal changes (2-8-years) in daily functioning (Clinical Dementia Rating-Sum of Boxes [CDR-SB]), global cognition (Montreal Cognitive Assessment [MoCA]), and 5 domain-specific cognitive indices. For risk-stratification, baseline plasma pTau217 status was defined using an amyloid PET-derived, LBD-specific cut-point to examine whether participants with abnormal levels demonstrated faster clinical progression in separate linear-mixed effects and survival models.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A total of 501 participants (mean[SD] age = 71.1[8.5]; 51.5% female) were included across LBD (\n                    <jats:italic>n<\/jats:italic>\n                    = 131), AD (\n                    <jats:italic>n<\/jats:italic>\n                    = 133), and HC (\n                    <jats:italic>n<\/jats:italic>\n                    = 237) groups. In LBD, higher baseline plasma pTau217 was associated with faster CDR-SB increase (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    = 0.30; 95% CI: [0.14, 0.45];\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), MoCA decline (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    = \u22120.35; 95% CI: [\u22120.57, \u22120.13];\n                    <jats:italic>p<\/jats:italic>\n                    = 0.002), and cognitive index decline (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2264 0.028). Participants with abnormal baseline pTau217 had a 0.85 points\/year faster CDR-SB increase (95% CI: [0.56, 1.15];\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), 0.87 points\/year faster MoCA decline (95% CI: \u22121.38, \u22120.37;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.001), faster decline on cognitive indices (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2264 0.018), and a three-fold higher risk of diagnostically progressing to MCI or dementia (HR = 3.41; 95% CI: [1.60, 7.28];\n                    <jats:italic>p<\/jats:italic>\n                    = 0.002) compared to participants with normal pTau217. Faster longitudinal pTau217 increase was associated with faster CDR-SB increase (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    = 0.24; 95% CI: [0.10, 0.38];\n                    <jats:italic>p<\/jats:italic>\n                    = 0.003).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Plasma pTau217 is a promising prognostic, risk-stratification, and monitoring biomarker of clinical progression in LBD, underscoring its utility for clinical practice and trials in mixed pathology groups.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.26.26349399","type":"posted-content","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:10:50Z","timestamp":1774656650000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma pTau217 as a Prognostic, Risk-Stratification, and Monitoring Biomarker of Clinical Progression in Lewy Body Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-5979","authenticated-orcid":false,"given":"S. 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