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Publication
medRxiv

Plasma Proteomic Networks Reveal Shared Biology with Brain Linked to Alzheimer’s Disease Pathology

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  • June 2, 2026
Topic/Product:
Alzheimer's, CNS, CNS Disease Panel 120
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

Alzheimer’s disease (AD) drives widespread molecular changes beyond the brain that are increasingly detectable in plasma. To map plasma proteomic signatures of AD in a broadly unbiased manner with high depth and reproducibility, we profiled plasma from 214 individuals spanning cognitively normal controls, mild cognitive impairment, and AD using microbead-based enrichment and data-independent acquisition mass spectrometry (DIA-MS). We reliably quantified 5,823 proteins across samples, and network analysis identified 29 plasma modules enriched for functions related to lipid metabolism, extracellular matrix remodeling, immune signaling, mitochondrial function, and proteostasis. Several modules were associated with cognition, APOE4, sex, race, and cerebrospinal fluid (CSF) amyloid and tau biomarkers. Among 129 individuals with paired CSF and plasma biomarker measurements, over 1,500 proteins differed between CSF biomarker–positive and –negative groups, including amyloid-linked matrisome proteins such as SMOC1, FRZB, SPON1 and CTHRC1. A 10-protein plasma panel classified CSF biomarker positivity with performance similar to plasma pTau217 (AUC = 0.91), and combining both improved accuracy (AUC = 0.99). Integration with a human brain proteomic network revealed that two-thirds of plasma modules were preserved in brain, with many AD-altered modules changing concordantly across compartments. This study establishes a scalable DIA-MS plasma proteomics platform that captures systemic and brain-linked AD biology and identifies complementary biomarkers beyond phosphorylated tau.

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Authors and Affiliations

Qi Guo1,2,3, Lingyan Ping1,2,3, Saima Rathore5, Duc M. Duong1,2,3, Anantharaman Shantaraman1,2,3, Edward J. Fox1,2,3, Erik C.B. Johnson2,3,4, James J. Lah2,3,4, Allan I. Levey*2,3,4 and Nicholas T. Seyfried*1,2,3 

1 Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA 30322, USA.

2 Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322, USA.

3 Goizueta Alzheimer’s Disease Research Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.

4 Department of Neurology, School of Medicine, Emory University, Atlanta, GA 30322, USA.

5 Department of Biomedical Informatics, School of Medicine, Emory University, Atlanta, GA 30322, 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.