Alzheimer’s disease biological PET staging using plasma p217+tau

作者：Azadeh Feizpour, Vincent Doré, Natasha Krishnadas, Pierrick Bourgeat, James D. Doecke, Ziad S. Saad, Gallen Triana‐Baltzer, Simon M. Laws, Rosita Shishegar, Kun Huang, Christopher Fowler, Larry D. Ward, Colin L. Masters, Jürgen Fripp, Hartmuth C. Kolb, Victor L. Villemagne, Christopher C. Rowe · 发表于：Communications Medicine · 年份：2025 · DOI：10.1038/s43856-025-00768-z · 被引用次数：9 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、S100 Proteins and Annexins

Abstract Background Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s disease (AD) neuropathology. However, their ability to substitute for tau PET to identify AD biological stage is unclear. Methods Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, 18 F-NAV4694 Aβ-PET (A) and 18 F-MK6240 tau-PET (T) data. Biological PET stages were defined according to the Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease (2024): Initial (A + T-), Early (A + T MTL + ), Intermediate (A + T MOD + ), and Advanced (A + T HIGH + ). The threshold for A+ was 25 Centiloid and for T HIGH + , the 75th percentile SUVR temporo-parietal in A + CI. Sixty percent were A + , 36% Intermediate/Advanced, and 9% Advanced. The performance of p217+tau in discriminating AD stages was assessed using Receiver Operating Characteristic (ROC) analysis and logistic regression. Results Plasma p217+tau concentrations increase across the AD biological PET stages, except between Initial and Early stages. Screening for all AD stages ( vs . A-T-), combined Intermediate/Advanced stages, or Advanced stage yields AUC of 0.92, 0.92, and 0.91, respectively (CI only: AUC 0.93, 0.89, 0.83). Plasma p217+tau Youden threshold provides sensitivity of 0.77 [0.73–0.90], specificity 0.91 [0.80–0.95], PPV 0.84 [0.71–0.89], and NPV 0.88 [0.85–0.93] for combined Intermediate/Advanced stages. For the Adv...