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Alzheimer’s & Dementia

GPND-AI NULISA: A 15-Protein AI classifier for diagnosis and co-pathology profiling across neurodegenerative diseases

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  • April 28, 2026
  • Carlos Cruchaga, et al., Washington University in St Louis
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Dementia
Sample Type:
Plasma

Abstract

INTRODUCTION

Accurate clinical diagnosis of neurodegenerative diseases remains challenging, particularly when individuals have mixed pathologies. We implemented the generalizable protein-based neurodegenerative disease artificial intelligence (GPND-AI) classifier using the NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) central nervous system (CNS) panel to classify Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, dementia with Lewy bodies, and healthy controls, while disentangling mixed pathologies.

METHODS

Proteomic and clinical information from the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (Knight-ADRC) and Movement Disorder Clinic were used to train and test the GPND-AI classifier. External validation was performed in a Banner Sun Health Research Institute cohort and additional Knight-ADRC samples with neuropathologically confirmed diagnoses.

RESULTS

GPND-AI identified 15 proteins that achieve an area under the curve (AUC) of 0.955 and 92.3% accuracy across five diagnostic categories. In validation cohort, predicted co-pathologies significantly correlated with clinical characteristics.

DISCUSSION

GPND-AI identified a 15-protein panel that accurately classifies individuals across the four major neurodegenerative diseases. Validation against neuropathology-confirmed diagnoses supports the utility of proteomics-based approaches for mapping disease-specific and co-existing neurodegenerative processes.

Highlights

  • A streamlined 15-protein NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) plasma panel accurately distinguished four major neurodegenerative diseases and healthy brain aging.
  • In an independent external cohort, the NULISA classifier distinguished the neurodegenerative diseases as defined by neuropathology.
  • Individual-level probability outputs capture early, ambiguous, and mixed pathological signatures, aligning with underlying amyloid/tau burden and cognitive decline.
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Authors & Affiliations

Ying Xu¹², Marisa N. Denkinger³, Menghan Liu¹², Katherine Gong¹², Yike Chen¹², Daniel Western¹², Jigyasha Timsina¹², Yuchen Cheng¹², Yunchang Xie¹², Rui Mu¹², John Budde¹², Thomas G. Beach³, Geidy E. Serrano³, Eric M. Reiman⁴, Alpana Singh³, Isabel Alfradique-Dunham⁵, Tammie L. S. Benzinger⁶⁷⁸, Suzanne E. Schindler⁵⁸⁹, John C. Morris⁵⁸, David M. Holtzman⁵⁸⁹, Joel S. Perlmutter⁵⁷¹⁰, B. Joy Snider⁵, Meghan C. Campbell⁵⁷, Paul T. Kotzbauer⁵, Nicholas J. Ashton³⁴¹¹, and Carlos Cruchaga¹²⁵⁶⁸⁹

¹ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
² NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA
³ Banner Sun Health Research Institute, Sun City, Arizona, USA
⁴ Banner Alzheimer’s Institute, Phoenix, Arizona, USA
⁵ Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA
⁶ Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
⁷ Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
⁸ Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA
⁹ Hope Center for Neurologic Disorders, Washington University, St. Louis, Missouri, USA
¹⁰ Department of Neuroscience Programs in Occupational Therapy and Physical Therapy, Washington University School of Medicine, St. Louis, Missouri, USA
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Västergötland, Sweden

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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.