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Alzheimer’s & Dementia

Biomarker Discovery in Alzheimer’s and Neurodegenerative Diseases using Nucleic Acid-Linked Immuno-Sandwich Assay

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  • May 22, 2025
  • Nicholas Ashton, et al.  - University of Gothenburg, Banner Health
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
CSF, Plasma, Serum

INTRODUCTION

Recent advancements in immunological methods accurately quantify biofluid biomarkers for Alzheimer’s disease (AD) pathology. Despite progress, more biomarkers, ideally in blood, are needed for effective disease monitoring for AD and other neurodegenerative proteinopathies.

METHODS

We used the Nucleic Acid Linked Immuno-Sandwich Assay (NULISA) central nervous system panel for biomarker quantification in plasma, serum, and cerebrospinal fluid of patients with AD, mild cognitive impairment, Lewy body dementia, progranulin (GRN) mutation carriers.

RESULTS

NULISA identified phosphorylated tau217 and neurofilament light chain as the most deregulated biomarkers in the AD continuum and GRN mutation carriers, respectively. Importantly, numerous novel proteomic changes were observed in each disease endophenotype, which included synaptic processing, inflammation, microglial reactivity, TAR DNA-binding protein 43, and α-synuclein pathology.

DISCUSSION

We underline the potential of next-generation biomarker identification tools to detect novel proteomic features that also incorporate established biomarkers. These findings highlight the importance of continued biomarker discovery to improve treatment decisions and help us better understand the complexities of neurodegenerative disorders.

Highlights

  • The, direct, or indirect, measures in blood that complement phosphorylated tau (p-tau)217 for other proteinopathies or disease progression are urgently needed.
  • Significant novel proteomic changes were observed in each disease endophenotype in plasma, serum, and cerebrospinal fluid, which included proteins involved in synaptic processing, inflammation, microglial reactivity, TAR DNA-binding protein 43, and α-synuclein pathology.
  • Nucleic Acid Linked Immuno-Sandwich Assay continued to unbiasely highlight p-tau217 and neurofilament light chain as the most significantly deregulated blood biomarkers in the Alzheimer’s disease continuum and progranulin mutation carriers, respectively
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Authors & Affiliations

Nicholas J. Ashton1,2,3*, Andrea L. Benedet1*, Guglielmo Di Molfetta1, Ilaria Pola1, Federica Anastasi4,5, Aida Fernández-Lebrero4,5,6,7, Albert Puig-Pijoan4,6,8, Ashvini Keshavan9, Jonathan Schott9,10, Kubra Tan1, Laia Montoliu-Gaya1, Richard Isaacson11,12, Matilde Bongianni13, Chiara Tolassi14, Valentina Cantoni15, Antonella Alberici15, Alessandro Padovani15,16,17,18, Gianluigi Zanusso19, Andrea Pilotto15,16,17,18, Barbara Borroni15,16, Marc Suárez-Calvet4,5,6,20, Kaj Blennow1,21,22,23, Henrik Zetterberg1,9,10,21,24,25

1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; 2 Banner Alzheimer’s Institute and University of Arizona, Phoenix, AZ, USA; 3 Banner Sun Health Research Institute, Sun City, AZ 85351, USA; 4 Hospital del Mar Research Institute, Barcelona, Spain; 5 Barcelona β eta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; 6 Servei de Neurologia, Hospital del Mar, Barcelona, Spain;7 Department of Medicine and Life Sciencesces, Universitat Pompeu Fabra, Barcelona, Spain; 8 Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 9 Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK; 10 UK Dementia Research Institute at UCL, London, UK; 11 Department of Neurology, Weill Cornell Medicine and New York – Presbyterian, New York, New York; 12 Department of Neurology, Florida Atlantic University, Charles E. Schmidt College of Medicine, Boca Raton, Florida; 13 Department of Neurosciences, Biomedicine, and Movement Sciences, Policlinico G. B. Rossi, University of Verona, 37134, Verona, Italy; 14 Clinical Investigation in Laboratory, Maggiore Hospital ASST-Crema, Crema, Italy; 15 Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy; 16 Department of Continuity of Care and Frailty, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili, Brescia, Italy; 17 Laboratory of Digital Neurology and Biosensors, University of Brescia, Brescia, Italy; 18 Brain Health Center, University of Brescia, Brescia, Italy; 19 Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; 20 Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain; 21 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; 22 Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; 23 Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China; 24 Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; 25 Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA  

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Steve Williams, MD, PhD

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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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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.