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Publication
medRxiv

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

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  • December 11, 2025
  • Mitchell Lai, et al., National University of Singapore
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

INTRODUCTION We evaluated the performance of plasma brain-derived (BD)-as well as total-p-tau181, p-tau217 and p-tau231 in detecting beta-amyloid positivity (Aβ+) and cognitive decline in a Singapore-based cohort of older people with cerebrovascular disease.

METHODS Brain amyloid status (Aβ-[n = 139] vs Aβ+ [n = 74]) was determined by assessment of positron emission tomography (PET) scans. Plasma BD and total p-tau were measured using NUcleic acid Linked Immuno-Sandwich Assay multiplexing platform (NULISAseq).

RESULTS BD-p-tau217 (area under the curve [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 three-range or binary references, BD-p-tau217 demonstrated high sensitivity (>90%), specificity (>90%), positive (>85%) and negative (>95%) predictive values. BD-p-tau217-derived high-risk group exhibited faster cognitive decline than the low-risk group.

DISCUSSION Risk stratification for PET Aβ+ based on plasma BD-p-tau217 suggests superior diagnostic and prognostic utility, warranting further assessment.

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Authors & Affiliations

Joyce R. Chong¹²³, Saima Hilal¹²⁴, Narayanaswamy Venketasubramanian⁵, Michael Schöll⁶⁷, Kaj Blennow⁶⁸⁹, Nicholas J. Ashton⁶¹⁰, Henrik Zetterberg³⁶⁷⁸¹¹, Christopher P. Chen¹², and Mitchell K. P. Lai¹²*

¹ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
² Memory, Aging and Cognition Centre, National University Health System, Singapore 117599, Singapore
³ Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
⁴ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore
⁵ Raffles Neuroscience Centre, Raffles Hospital, Singapore 188770, Singapore
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
⁷ Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
⁸ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
⁹ Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
¹⁰ Banner Sun Health Research Institute, Sun City, AZ, USA
¹¹ UK Dementia Research Institute at UCL, University College London, London, UK

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.