The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Topic/Product:
CNS, CNS Disease Panel 120
Disease Area:
Neurodevelopmental Disabilities (NDD)
Sample Type:
CSF, Plasma

Abstract

Introduction: Novel tools for absolute quantification of established and emerging fluid neurobiomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink™ Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer’s dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting transformation formula’s. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: – – – – The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Aβ42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.

Authors & Affiliations

Yanaika S. Hok-A-Hin1, Lisa Vermunt1, Natascha de Jong1, Marta del Campo Milan2,3, Everard Vijverberg4, Afina W. Lemstra4, Yolande A.L. Pijnenburg4, Argonde C. Van Harten4, Charlotte E. Teunissen1

1 Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands.

2 Barcelonaßeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.

3 Hospital del Mar Research Institute, Barcelona, Spain.

4 Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, The Netherlands.

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.