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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer's disease in clinical and community cohorts

Authors

Jun Wang, Shan Huang, Guoyu Lan, Yu-Jie Lai, Qing-Hua Wang, Yang Chen, Zhong-Song Xiao, Xiao Chen, Xian-Le Bu, Yu-Hui Liu, Fan Zeng, Laihong Zhang, Anqi Li, Yue Cai, Pan Sun, Zhengbo He, Vincent Doré, Jurgen Fripp, Pierrick Bourgeat, Qin Chen, Jin-Tai Yu, Yi Tang, Henrik Zetterberg, Colin L Masters, Tengfei Guo, Yan-Jiang Wang, Translational Biomarker Research of AgIng and Neurodegeneration (TBRAIN)

Abstract

Alzheimers Dement. 2025 Mar;21(3):e70038. doi: 10.1002/alz.70038.

ABSTRACT

INTRODUCTION: This study was undertaken to evaluate the diagnostic performance of a novel plasma phosphorylated tau (p-tau) 217/amyloid beta (Aβ) 42 ratio test for Alzheimer's disease (AD).

METHODS: The diagnostic performance of the Lumipulse G plasma p-tau217/Aβ42 ratio was evaluated using Aβ and tau positron emission tomography (PET) as reference standards in a clinic cohort (n = 391) and a community cohort (n = 121).

RESULTS: Plasma p-tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974), which were clinically equivalent to those of cerebrospinal fluid (CSF) p-tau181/Aβ42 and Aβ42/Aβ40 and higher than those of blood p-tau217, Aβ42/Aβ40, p-tau181, and p-tau181/Aβ42 in both clinic and community cohorts. Applying a two-cutoff approach improved the specificity without reducing sensitivity. The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts.

DISCUSSION: Plasma p-tau217/Aβ42 has high performance in detecting cerebral AD pathologies, thus offering a promising tool for clinical diagnosis and community screening of AD.

HIGHLIGHTS: Lumipulse G plasma p-tau217 and the p-tau217/Aβ42 ratio accurately identified abnormal Aβ and tau PET statuses in both clinical and community cohorts. The performance of plasma p-tau217 and p-tau217/Aβ42 ratio were equivalent to CSF tests. Plasma p-tau217/Aβ42 ratio outperformed p-tau217 alone in identifying Aβ PET positivity, and this superiority is more obvious in the community cohort, suggesting an advantage in the early diagnosis of AD. Two cut points of p-tau217/Aβ42 were established in the Chinese population for clinical laboratory and community screening uses.

PMID:40156286 | DOI:10.1002/alz.70038

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg