Double cutoff strategies for plasma pTau217 to predict Tau PET positivity across multiple assay platforms: Tau-enriched and Tau-scarce cohorts for cost-effective clinical use
Year: 2026
Type: article
Abstract: BACKGROUND: We aimed to evaluate whether double cutoff strategies for plasma pTau217 across multiple assay platforms improve tau PET positivity prediction compared with single cutoffs and support cost-effective clinical use. METHODS: We analyzed two cohorts: K-ROAD (n = 120; tau-enriched) and NA-ADNI (n = 280; tau-scarce). Tau PET positivity was defined within the temporal meta-ROI as SUVR > mean + 2 SD of Aβ-negative CU. Single and double cutoffs were compared for accuracy and misclassification-related costs. RESULTS: Single cutoffs showed good accuracy across most assays (AUCs > 0.80), except for C2N ratio. Double cutoffs modestly improved accuracy but expanded intermediate groups, in the tau-scarce cohort. Cost analyses revealed assay- and cohort-specific effects, with reductions in most settings but increases for Lilly-MSD and Janssen-Simoa. CONCLUSION: Double cutoff strategies should be applied with attention to assay platform and cohort context. Accuracy gains were modest, but clinical utility lies in reducing misclassification costs and guiding confirmatory PET use.
Source: Alzheimer s Research & Therapy
Authors: Heekyoung Kang, Yuna Gu, Jungah Lee, Soyeon Yoon, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Theresa A. Day, Michael W. Weiner, Daeun Shin, Sohyun Yim, Seonghyeon Kim, Hee Kyung Park, Min Young Chun, Eun Hye Lee, Jun Pyo Kim, Hee Jin Kim, Duk L. Na, Hyemin Jang, Sang Won Seo, for the ADNI and K-ROAD study group
Institutions: Samsung Medical Center, Sungkyunkwan University, University of Wisconsin–Madison, Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg, University of Science and Technology of China, Sorbonne Université, Pitié-Salpêtrière Hospital, Institut du Cerveau, University of Arizona, Stavanger University Hospital, Banner Sun Health Research Institute, Banner Alzheimer’s Institute, Eli Lilly (United States), University of California, San Francisco, Yonsei University, Yonsei University Health System, Yongin Severance Hospital, Indiana University Indianapolis, Indiana University School of Medicine, Asan Medical Center, University of Ulsan
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
OpenAlex ID: W7123501245