Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification

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<sub>BD-pTau217</sub> = 0.02 to 0.06, ρ<sub>Total-pTau217</sub> = 0.06 to 0.12) and creatinine (ρ<sub>BD-pTau217</sub> = 0.03 to 0.08, ρ<sub>Total-pTau217</sub> = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (ρ<sub>BD-pTau217</sub> = 0.78 to 0.80, ρ<sub>Total-pTau217</sub> = 0.74 to 0.77) and exhibits superior classification performance for amyloid-β (Aβ) pathology (area under the curve [AUC]<sub>BD-pTau217</sub> = 0.96 to 0.98, AUC<sub>Total-pTau217</sub> = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the Aβ-positive group (AUC<sub>BD-pTau217</sub> = 0.89, AUC<sub>Total-pTau217</sub> = 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.

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Journal
Proceedings of the National Academy of Sciences
Published
2026-03-02
DOI
https://doi.org/10.1073/pnas.2536792123
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification

Zengjie Xia, Wan Wa Wong, Yuanbing Jiang, KS Ho et al.
Proceedings of the National Academy of Sciences
Alzheimer's disease research and treatments
article

Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification

Zengjie Xia, Wan Wa Wong, Yuanbing Jiang, KS Ho, Nancy Y. Ip, Wenyue Zheng, Ching Yu Lam, Timothy C Y Kwok, Yat Fung Shea, Vincent C. T. Mok, Kin Ying Boniface MOK, Hiu Yi Wong, Lily K. W. Cheng, Chun Keung Shum, Jacqueline K. Y. Yuen, Hok Man Wai, Andrew L. T. Chan, Siu Man Choi, Fanny C. Ip, Henrik Zetterberg
article en

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<sub>BD-pTau217</sub> = 0.02 to 0.06, ρ<sub>Total-pTau217</sub> = 0.06 to 0.12) and creatinine (ρ<sub>BD-pTau217</sub> = 0.03 to 0.08, ρ<sub>Total-pTau217</sub> = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (ρ<sub>BD-pTau217</sub> = 0.78 to 0.80, ρ<sub>Total-pTau217</sub> = 0.74 to 0.77) and exhibits superior classification performance for amyloid-β (Aβ) pathology (area under the curve [AUC]<sub>BD-pTau217</sub> = 0.96 to 0.98, AUC<sub>Total-pTau217</sub> = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the Aβ-positive group (AUC<sub>BD-pTau217</sub> = 0.89, AUC<sub>Total-pTau217</sub> = 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.

Proceedings of the National Academy of SciencesVol. 123(10)
University of Science and Technology of China (CN), Hospital Authority (HK), University of Wisconsin–Madison (US), Chinese University of Hong Kong (HK), Sahlgrenska University Hospital (SE), United Christian Hospital (CN), German Center for Neurodegenerative Diseases (DE), HKUST Shenzhen Research Institute (CN), Queen Elizabeth Hospital (GB), Tang Shiu Kin Hospital (CN), Institute for Neurodegenerative Disorders (US), UK Dementia Research Institute (GB), MRC Prion Unit (GB), Shenzhen Institutes of Advanced Technology (CN), University College London (GB), Indian Institute of Science Bangalore (IN), University of Gothenburg (SE), University of Hong Kong (HK)
University of Wisconsin-Madison, Indian Institute of Science, Lui Che Woo Institute of Innovative Medicine, University College London, University of Hong Kong, Chinese University of Hong Kong, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Hong Kong University of Science and Technology, Shenzhen-Hong Kong Institute of Brain Science, School of Medicine and Public Health, University of Wisconsin-Madison, Shenzhen Research Institute, City University of Hong Kong, Sahlgrenska Akademin
Openalex Percentile: Top 37%
Alzheimer's disease research and treatments
DOIOpen Access PDFOpenAlex
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