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Alzheimer’s & Dementia

Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis

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  • July 4, 2025
  • Bedia Samanci, et al. Istanbul University
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Dementia
Sample Type:
Plasma

Abstract

INTRODUCTION

Diagnosing Alzheimer’s disease (AD) is challenging due to overlapping symptoms with other dementias and the invasiveness of current biomarkers. This study introduces the NULISA platform, a novel proteomics technology, to evaluate diagnostic accuracy of known biomarkers and uncover novel biomarkers underlying different dementias.

METHODS

We analyzed plasma and cerebrospinal fluid (CSF) samples from 248 participants diagnosed with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and mild cognitive impairment (MCI). Plasma biomarkers were evaluated using regression models, receiver operating characteristics curve (ROC) analysis, and pathway enrichment.

RESULTS

Plasma phosphorylated Tau217 (pTau217) demonstrated the highest diagnostic accuracy for AD, DLB, and FTD (area under the curve [AUCs]: 0.9, 0.84, and 0.79, respectively). CXCL1 (fractalkine), synaptosomal-associated protein 25 (SNAP25), triggering receptor expressed on myeloid cells 1 (TREM1), β-synuclein, and tyrosine kinase (TEK) are expressed differently in DLB and FTD than AD. Ingenuity pathway analyses revealed astrocytic, synaptic, and inflammatory pathways as shared and distinct mechanisms across these dementia types.

CONCLUSION

Our findings establish plasma pTau217 as a robust diagnostic marker. This study provides new plasma biomarkers for differential diagnosis of dementias with a noninvasive method.

Highlights

  • Plasma pTau217 showed high diagnostic accuracy for AD, DLB, and FTD.
  • CXCL1, SNAP25, TREM1, β-synuclein, and TEK are novel markers distinguishing other dementias from AD.
  • Noninvasive plasma biomarkers enable diagnosis and differentiation of dementias.
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Authors & Affiliations

Hasim Gezegen1,2 Merve Alaylıo˘glu3 Erdi ¸Sahin2 Owen Swann1Elena Veleva1 Gamze Güven4 Umran Yaman1 Dervi¸s A. Salih1,5 Ba¸sar Bilgiç2Ha¸smet Hana˘gası2 Hakan Gürvit2 Murat Emre2 Duygu Gezen-Ak3Erdinç Dursun3 Henrik Zetterberg1,5,6,7,8,9 John Hardy1,5,8 Amanda Heslegrave1,5Maryam Shoai1,5 Bedia Samanci2

  1. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
  2. Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey
  3. Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa,Istanbul, Turkey
  4. Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
  5. UK Dementia Research Institute at UCL, London, UK
  6. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal,Sweden
  7. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  8. Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China9 Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison,Wisconsin, USA
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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.