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Alzheimer’s & Dementia

Dissecting Alzheimer’s proteomic landscape through NULISA profiling of brain cell-specific extracellular vesicles

  • August 22, 2026
  • Gagan Deep, et al., Wake Forest SOM
Product:
CNS Disease Panel 120
Topic:
Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma-EVs
Back to Publications​
  • August 22, 2026
Product:
CNS Disease Panel 120
Topic
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma-EVs

Abstract

INTRODUCTION

Blood-based biomarkers are essential for early detection, monitoring, and therapeutic development in Alzheimer’s disease (AD) and related dementia (ADRD), but current assays lack brain cell specificity and sensitivity to low-abundant proteins.

METHOD

We isolated the following brain cell-derived small extracellular vesicles (sEV) from the plasma of individuals with normal cognition (CN), mild cognitive impairment (MCI), or ADRD: neurons (NDE), astrocytes (ADE), microglia (MDE), oligodendrocytes (ODE), pericytes (PDE), and endothelial cells (EDE). Using NULISAseq, we profiled 122 proteins, spanning AD pathology, neurodegeneration, and neuroinflammation.

RESULTS

sEV proteomes showed distinct brain cell-type-specific signatures. MCI exhibited early dysregulation of neuroprotective, inflammatory, and vascular markers in NDE, MDE, and ODE. ADRD displayed broader alteration tau, amyloid, neuroinflammation, vascular dysfunction, and synaptic loss across multiple sEV populations.

DISCUSSION

Combining NULISAseq with brain cell-derived plasma sEV enables the detection of multicellular molecular changes in ADRD, supporting their use as a minimally invasive platform for biomarker discovery.

Highlights

  • Ultrasensitive NULISAseq profiling was applied to six brain cell-derived sEV subtypes.
  • Neuronal and astrocytic sEV showed strong enrichment of total and p-tau.
  • Microglial, oligodendrocyte, and vascular sEV captured inflammatory changes.
  • sEV-based proteomics identify cell-specific signatures across CN, MCI, and ADRD.
  • This study demonstrates a multicellular liquid-biopsy framework for ADRD biomarker discovery.
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Authors and Affiliations

Ashish Kumar¹, Mitu Sharma¹, Yixin Su¹, Sangeeta Singh¹, Jordan E. Tanley¹, Ramon Casanova², Fang-Chi Hsu²˒³, Suzanne Craft¹˒⁴, Michelle M. Mielke¹˒⁴˒⁵, Timothy M. Hughes¹˒⁴˒⁵, and Gagan Deep¹˒³˒⁴

¹ Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
² Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
³ Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
⁴ Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
⁵ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 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.