Plasma brain-derived p-Tau217 outperforms other p-Tau species in detecting abnormal brain amyloid in an Asian cohort of older people with cerebrovascular disease burden - 28/05/26

Doi : 10.1016/j.tjpad.2026.100615

Joyce R. Chong ^a,^b,^c,^⁎ , Saima Hilal ^a,^b,^d, Narayanaswamy Venketasubramanian ^e, Michael Schöll ^f,^g, Nicholas J. Ashton ^f,^h, Henrik Zetterberg ^c,^f,^g,ⁱ, Christopher P. Chen ^a,^b, Mitchell K.P. Lai ^a,^b,^⁎

^a Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore

^b Memory, Aging and Cognition Centre, National University Health Systems, Singapore 117599, Singapore

^c Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA

^d Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore

^e Raffles Neuroscience Centre, Raffles Hospital, Singapore 188770, Singapore

^f Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

^g Dementia Research Centre, Institute of Neurology, University College London, London, UK

^h Banner Sun Health Research Institute, Sun City, Arizona, USA

ⁱ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France

^⁎ Corresponding Authors. Joyce R. Chong, Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA ^⁎⁎ Mitchell K.P. Lai, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, Singapore, 117599 Singapore Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive Singapore 117599 Singapore

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Abstract

BACKGROUND

Plasma brain derived-p-Tau217 (BD-p-Tau217) may outperform total-p-Tau217 in detecting brain amyloid burden and warrants evaluation.

OBJECTIVES

To perform head-to-head comparison of plasma BD- as well as total-p-Tau181, p-Tau217 and p-Tau231 for detecting beta-amyloid positivity (Aβ+), evaluate reference ranges for Aβ+, and assess the prognostic utility of BD-p-Tau217 reference ranges.

DESIGN

Observational study.

SETTING

Participants recruited from memory clinics and the community in Singapore.

PARTICIPANTS

213 participants, including 44 cognitively normal, 107 cognitively impaired no dementia, and 62 dementia (mean [SD] age, 73 [ 1 ] years; 121 females).

MEASUREMENTS

Amyloid status (Aβ- [n = 139] vs Aβ+ [n = 74]) was determined by positron emission tomography (PET). Plasma BD-p-Tau and total-p-Tau were measured using the NULISAseq™ CNS Disease Panel 120. The diagnostic performance for detecting Aβ+, reference ranges (three-range: 95% specificity/95% sensitivity); binary: maximizing Youden index), and the prognostic performance of p-Tau biomarkers were evaluated.

RESULTS

Plasma BD-p-Tau217 (AUC = 0.965) outperformed other BD- and total-p-Tau species in detecting PET Aβ+ (AUC = 0.823–0.937; all p ≤ 0.008). Using a three-range reference, BD-p-Tau217 achieved positive predictive value (PPV) and negative predictive value (NPV) of 90% and 97%, respectively. Proportion of participants in the intermediate-risk group was 7% (n=14). Applying a binary reference, BD-p-Tau217 achieved both a specificity and sensitivity of 92%, with PPV and NPV of 86% and 96%, respectively. BD-p-Tau217-derived high-risk group exhibited faster cognitive decline than the low-risk group.