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Alzheimer’s & Dementia

Targeted blood proteome profiling using NULISAseq identifies a high-performance biomarker panel for Aβ pathology quantification and staging

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  • January 4, 2026
  • Nancy Ip, et al., Hong Kong University of Science and Technology
Topic/Product:
CNS Disease Panel 120, Inflammation Panel 250, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

INTRODUCTION

While current blood-based biomarkers for Alzheimer’s disease (AD) are effective for determining amyloid beta (Aβ) pathology positivity/negativity, they are insufficient for quantifying Aβ plaque deposition.

METHODS

We profiled 325 plasma proteins in a Hong Kong Chinese cohort using the Nucleic Acid Linked Immuno‑Sandwich Assay (NULISAseq) platform. We analyzed the dysregulation trajectories of the blood proteome along Aβ pathology progression and used machine learning to develop a biomarker panel to quantify Aβ pathology.

RESULTS

We identified 43 blood proteins correlated with Aβ plaque accumulation and selected 8 proteins to construct a model. This model was strongly correlated with amyloid positron emission tomography Centiloid values (r = 0.89), enabling quantification of Aβ deposition and classification of early-stage pathology (area under the curve = 0.93).

DISCUSSION

This study provides a systematic profile of dynamic protein alterations during Aβ pathology progression. Moreover, we developed a biomarker assay that accurately quantifies Aβ pathology, offering a potential tool to facilitate early screening and monitoring of amyloid pathology.

Highlights

  • Nucleic Acid Linked Immuno‑Sandwich Assay (NULISAseq) was applied to profile the blood proteome during the development of brain amyloid pathology.

  • Different immune and neuronal biological processes exhibit distinct and stage-specific dysregulation patterns during amyloid accumulation.

  • A machine learning–based, eight-protein blood biomarker panel was developed to accurately predict the quantitative extent of brain amyloid pathology.

  • The eight-protein biomarker assay accurately detects early amyloid accumulation and outperforms prediction based on phosphorylated tau 217 alone.

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Authors & Affiliations

Wenyue Zheng¹², Yuanbing Jiang¹², Hiu Yi Wong¹², Wan Wa Wong¹², Lily K. W. Cheng¹², Elaine Y. L. Cheng², Bonnie W. Y. Wong², Ronnie M. N. Lo², Siu Ki Leung², Fanny C. Ip¹²³, Jacqueline K. Y. Yuen⁴, Yat Fung Shea⁴, Wai Ming Wong⁵, Chun Keung Shum⁵, Hok Man Wai⁶, Vincent C. T. Mok⁷, Timothy C. Y. Kwok⁸, Kin Y. Mok¹²⁹, Amanda Heslegrave⁹¹⁰, John Hardy²⁹¹⁰, Henrik Zetterberg²⁹¹⁰¹¹¹²¹³¹⁴¹⁵, Amy K. Y. Fu¹²³¹⁶, and Nancy Y. Ip¹²³¹⁶

¹ 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, Hong Kong Special Administrative Region, China
² InnoHK Hong Kong Center for Neurodegenerative Diseases, Hong Kong Special Administrative Region, China
³ Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen–Hong Kong Institute of Brain Science, Shenzhen, Guangdong, China
⁴ Geriatrics Division, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
⁵ Department of Medicine and Geriatrics, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Tuen Mun, Hong Kong Special Administrative Region, China
⁶ Department of Medicine and Geriatrics, United Christian Hospital, Hospital Authority, Kwun Tong, Hong Kong Special Administrative Region, China
⁷ Lau Tat-chuen Research Centre of Brain Degenerative Diseases in Chinese, Gerald Choa Neuroscience Institute, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China
⁸ Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Geriatrics, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China
⁹ Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK
¹⁰ UK Dementia Research Institute, University College London, London, UK
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, The University of Gothenburg, Mölndal, Sweden
¹² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
¹³ Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
¹⁴ Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
¹⁵ Centre for Brain Research, Indian Institute of Science, Bangalore, India
¹⁶ Guangdong–Hong Kong Joint Laboratory for Psychiatric Disorders, Hong Kong Special Administrative Region, China

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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.