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<p>Multiple proteinopathies commonly coexist in neurodegenerative diseases, making it essential to evaluate plasma biomarker performance in these complex diseases. While plasma biomarkers accurately detect amyloid-β pathology in Alzheimer’s disease (AD), their performance is unknown in neuronal synuclein disease (NSD). We aimed to determine the accuracy of plasma pTau217, pTau181, Aβ42/40, GFAP, and NfL to detect amyloid-β in NSD, then establish and validate cut points for the most promising marker. We included 253 participants (180 discovery; 73 validation). In the discovery cohort, NSD status was defined by CSF α-synuclein seed amplification assay and amyloid-β status by CSF Aβ42/40. Participants included individuals with clinical Lewy body disease (LBD), AD, and cognitively unimpaired. Validation cohorts consisted of clinically diagnosed LBD participants. In the discovery cohort, plasma pTau217, pTau181, Aβ42/40, and GFAP significantly differed by amyloid-β status regardless of NSD status, while NfL was highest in NSD+/Aβ+ participants. Among all biomarkers, plasma pTau217 showed the best diagnostic performance (AUC = 0.92, 95% CI = 0.81–0.98). Applying plasma pTau217 cut points to pre-screen clinically diagnosed LBD participants reduced the need for confirmatory amyloid-β PET or CSF in 41-56%. These findings support plasma pTau217 as a minimally-invasive tool for identifying pathological amyloid-β in neuronal synucleinopathies with mixed Alzheimer’s disease pathology.</p>

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Plasma phosphorylated tau 217 detects amyloid-β in neuronal synuclein disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月10日

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  • Alena M. Smith,
  • Sara A. Lorkiewicz,
  • Burak Arslan,
  • Laia Montoliu-Gaya,
  • Nicholas J. Ashton,
  • Edward N. Wilson,
  • Daniel Alcolea,
  • Íñigo Rodríguez-Baz,
  • Juan Fortea,
  • Christina B. Young,
  • Joseph R. Winer,
  • Marian Shahid-Besanti,
  • Hillary Vossler,
  • Melanie J. Plastini,
  • Tianyu Pan,
  • Elena Vera-Campuzano,
  • Isabel Sala,
  • Justin H. Mendiola,
  • Veronica Ramirez,
  • Geoffrey A. Kerchner,
  • Katrin I. Andreasson,
  • Victor W. Henderson,
  • Thomas J. Montine,
  • Lu Tian,
  • Elizabeth C. Mormino,
  • Henrik Zetterberg,
  • Kathleen L. Poston,
  • Carla Abdelnour

摘要

Multiple proteinopathies commonly coexist in neurodegenerative diseases, making it essential to evaluate plasma biomarker performance in these complex diseases. While plasma biomarkers accurately detect amyloid-β pathology in Alzheimer’s disease (AD), their performance is unknown in neuronal synuclein disease (NSD). We aimed to determine the accuracy of plasma pTau217, pTau181, Aβ42/40, GFAP, and NfL to detect amyloid-β in NSD, then establish and validate cut points for the most promising marker. We included 253 participants (180 discovery; 73 validation). In the discovery cohort, NSD status was defined by CSF α-synuclein seed amplification assay and amyloid-β status by CSF Aβ42/40. Participants included individuals with clinical Lewy body disease (LBD), AD, and cognitively unimpaired. Validation cohorts consisted of clinically diagnosed LBD participants. In the discovery cohort, plasma pTau217, pTau181, Aβ42/40, and GFAP significantly differed by amyloid-β status regardless of NSD status, while NfL was highest in NSD+/Aβ+ participants. Among all biomarkers, plasma pTau217 showed the best diagnostic performance (AUC = 0.92, 95% CI = 0.81–0.98). Applying plasma pTau217 cut points to pre-screen clinically diagnosed LBD participants reduced the need for confirmatory amyloid-β PET or CSF in 41-56%. These findings support plasma pTau217 as a minimally-invasive tool for identifying pathological amyloid-β in neuronal synucleinopathies with mixed Alzheimer’s disease pathology.