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Alzheimer’s & Dementia

Inflammation biomarkers and Alzheimer’s disease: A pilot study using NULISAseq

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  • January 30, 2025
  • Guglielmo Di Molfetta, et al. University of Gothenburg
Topic/Product:
Inflammation Panel 250, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Serum

Abstract

INTRODUCTION

Increasing evidence links amyloid beta (Aβ) aggregation with inflammation. This pilot study investigated the use of an immunoassay panel to map biomarker changes in patients with Alzheimer’s disease (AD). Furthermore, we evaluated the stability of protein quantification after multiple freeze–thaw cycles (FTCs).

METHODS

The nucleic acid-linked immuno-sandwich assay (NULISA) inflammation panel measured 203 proteins in serum samples of individuals with (n = 31) and without (n = 31) AD pathology. Linear models, adjusted for age and sex, contrasted protein expression across groups.

RESULTS

After multiple-testing adjustments, glial fibrillary acidic protein (p < 0.001) and S100A12 (p < 0.001) were significantly changed in the presence of AD pathology. Furthermore, they correlated with cerebrospinal fluid biomarkers (phosphorylated tau-181 [p-tau181], tau, and Aβ42). Additional markers were nominally changed between groups. Five FTCs caused minimal changes in measurements with the NULISA inflammation panel.

DISCUSSION

Monitoring of inflammation in AD, using the 200-plex NULISA panel, demonstrates changes in peripherally circulating inflammation-related proteins. Contrary to previous reports, FTCs had minimal impact on the quantification of inflammatory markers.

Highlights

  • The novel nucleic acid-linked immuno-sandwich assay (NULISA) inflammation panel, which includes 200 protein biomarkers, was used.
  • The panel was used for the first time in serum from patients with Alzheimer’s disease (AD).
  • The protein S100A12 was identified as a potential biomarker for AD.
  • Inflammation markers were stable in up to five freeze–thaw cycles.
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Authors & Affiliations

Guglielmo Di Molfetta1; Ilaria Pola1; Kubra Tan1; Richard Isaacson2,3; Kaj Blennow1,4,5,6; Nicholas J. Ashton1,7,8; Andrea L. Benedet1; Henrik Zetterberg1,4,9,10,11,12

  1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
  2. Department of Neurology, Weill Cornell Medicine and New York-Presbyterian, New York, New York, USA
  3. Department of Neurology, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA
  4. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  5. Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
  6. 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
  7. Banner Alzheimer’s Institute, University of Arizona, Phoenix, Arizona, USA
  8. Banner Sun Health Research Institute, Sun City, Arizona, USA
  9. Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
  10. Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison,Wisconsin, USA
  11. Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK
  12. UK Dementia Research Institute at UCL, 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.