Matrix matters: head-to-head concordance of serum and plasma for NULISAseq CNS Disease Panel

Product:

CNS Disease Panel 120

Topic:

CNS

Disease Area:

Alzheimer's Disease, Motor Neuron Disease, Multiple Sclerosis (MS)

Sample Type:

Plasma, Serum

Abstract

Blood-based proteomic profiling is now widely applied in neurodegenerative and neuroinflammatory disease, yet the choice between serum and plasma remains poorly characterised for high-multiplex platforms. Many legacy biobanks hold mainly serum, whereas most current NUcleic-acid-Linked Immuno-Sandwich Assay (NULISA) studies use plasma. We compared the 130-protein NULISAseq central nervous system (CNS) Disease Panel head-to-head in matched serum and plasma collected at the same draw from 62 participants (30 neurodegenerative, 19 demyelinating, 13 healthy controls). Agreement was measured with Spearman correlation (rho), Lin’s concordance correlation coefficient (CCC), the intraclass correlation coefficient (ICC) and the mean paired serum-to-plasma difference (dNPQ). Concordance was moderate to high: 123 of 130 proteins reached significance and 18 reached rho >= 0.90, with a median rho of 0.72 (range 0.10-0.988). Proteins fell into three tiers. Cytoskeletal markers (NEFH rho=0.988; NEFL rho=0.947) and glial GFAP (rho=0.949, |dNPQ|<0.5) were interchangeable between matrices. Phosphorylated tau (pTau) species retained excellent rank concordance but carried a systematic plasma-greater-than-serum offset (pTau-181 rho=0.869, dNPQ=+0.67; pTau-217 rho=0.846, dNPQ=+0.64; pTau-231 rho=0.885, dNPQ=+0.89). Platelet-derived analytes (CD40LG rho=0.102, dNPQ=-4.74; BDNF rho=0.223, dNPQ=-2.69) and intracellular synaptic proteins (NRGN, SNAP25, ENO2) diverged markedly. For most clinically relevant neurodegeneration markers, especially cytoskeletal and glial proteins, serum is a valid substitute for plasma; absolute thresholds for phosphorylated tau and amyloid peptides require matrix-specific calibration, and platelet-sensitive analytes cannot be compared across matrices without strictly standardised pre-analytical conditions.

Main Points

Across the 130-protein NULISAseq CNS Disease Panel, serum and plasma showed moderate-to-high overall concordance (median Spearman rho 0.72; 123/130 proteins significant).
Neurofilaments (NEFH, NEFL) and GFAP were interchangeable between matrices, whereas phosphorylated tau species retained rank order but required matrix-specific calibration of absolute levels.
Platelet-derived (CD40LG, BDNF) and intracellular synaptic proteins (NRGN, SNAP25, ENO2) were not comparable across matrices without strict pre-analytical standardisation.

Authors and Affiliations

Tommaso Merati¹˒²˒³*⊺, Chiara Tolassi¹˒²˒³⊺, Alessandro Rondina¹˒², Irene Girotto¹˒²˒³, Marianna Bertoni¹˒²˒³, Eileen Mac Sweeney¹˒²˒³, Andrea Toja¹˒²˒³, Eqrem Rusi¹˒²˒³, Caterina Martinuzzo¹˒²˒³, Andrea Pilotto¹˒²˒³˒⁴, and Alessandro Padovani¹˒²˒³˒⁵

¹ Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Italy
² Neurology Unit, ASST Spedali Civili Brescia University Hospital, Italy
³ Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Italy
⁴ Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences
⁵ Brain Health Center, University of Brescia, Italy

\* Corresponding author: Tommaso Merati
⊺ Tommaso Merati and Chiara Tolassi contributed equally to this work and share first authorship.

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.

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.