Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification
Abstract
Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker for accurately detecting Alzheimer’s disease (AD) pathology. However, interference from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic precision. Recently developed brain-derived pTau217 (BD-pTau217) assays emerge as highly specific tools for detecting AD-related pathological changes in the brain. In this study, we conducted a head-to-head comparison of the NULISAqpcr BD-pTau217 assay and Simoa ALZpath total p-Tau217 assay in two independent, amyloid-PET–characterized Chinese cohorts. Our results demonstrate a strong correlation between BD-pTau217 and total pTau217 (ρ = 0.89 to 0.90), with BD-pTau217 showing significantly reduced interference from kidney dysfunction, as evidenced by weaker associations with blood levels of urea (ρ BD-pTau217 = 0.02 to 0.06, ρ Total-pTau217 = 0.06 to 0.12) and creatinine (ρ BD-pTau217 = 0.03 to 0.08, ρ Total-pTau217 = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (ρ BD-pTau217 = 0.78 to 0.80, ρ Total-pTau217 = 0.74 to 0.77) and exhibits superior classification performance for amyloid-β (Aβ) pathology (area under the curve [AUC] BD-pTau217 = 0.96 to 0.98, AUC Total-pTau217 = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the Aβ-positive group (AUC BD-pTau217 = 0.89, AUC Total-pTau217 = 0.78), facilitating more accurate disease staging. These findings underscore BD-pTau217 as a highly sensitive and specific blood-based biomarker for AD that has significant potential for early detection, precise classification, and staging of AD-related brain pathology in clinical practice.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Yuanbing Jiang
Division of Life Science, State Key Laboratory of Nervous System Disorders, Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Wenyue Zheng
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Zengjie Xia
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Wan Wa Wong
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Lily K. W. Cheng
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Fanny C. Ip
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Siu Man Choi
Department of Medicine, Queen Elizabeth Hospital, Hospital Authority
Andrew L. T. Chan
Department of Medicine, Queen Elizabeth Hospital, Hospital Authority
Ching Yu Lam
Department of Medicine and Geriatrics Ruttonjee & Tang Shiu Kin Hospitals
Ka Shing Ho
Department of Medicine and Geriatrics, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority
Chun Keung Shum
Department of Medicine and Geriatrics, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority
Jacqueline K. Y. Yuen
Division of Geriatrics, Department of Medicine, School of Clinical Medicine, The University of Hong Kong
Yat Fung Shea
Division of Geriatrics, Department of Medicine, School of Clinical Medicine, The University of Hong Kong
Hok Man Wai
Department of Medicine and Geriatrics, United Christian Hospital, Hospital Authority
Vincent C. T. Mok
Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong
Timothy C. Y. Kwok
Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Geriatrics, Department of Medicine and Therapeutics, The Chinese University of Hong Kong
Kin Y. Mok
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Hiu Yi Wong
Division of Life Science, State Key Laboratory of Nervous System Disorders and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Henrik Zetterberg
Amy K. Y. Fu
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology
Nancy Y. Ip
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology