Benchmarking of a multi-biomarker low-volume panel for Alzheimer’s Disease and related dementia research

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

CSF, Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Alzheimer's Disease

Sample Type:

CSF, Plasma

Abstract

Alzheimer’s Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key. Accurate technologies are currently available for established biomarkers, mainly immunoassays and immunoprecipitation liquid chromatography-mass spectrometry (IP-MS), and some of them are already being used in clinical settings. Although some immunoassays- and IPMS based platforms provide multiplexing for several different coding proteins there is not a current platform that can measure all the stablished and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) is a mid-throughput platform with antibody based measurements with a sequencing output that requires 15μL of sample volume to measure more than 100 analytes, including those typically assayed for AD. Here we benchmarked and compared the AD-relevant biomarkers including in the NULISA against validated assays, in both CSF and plasma. Overall, we have found that CSF measures of Aß42/40, NfL, GFAP, and ptau217 are highly correlated and have similar predictive performance when measured by immunoassay, mass-spectrometry or NULISA. In plasma, p-tau217 shows a performance similar to that reported with other technologies when predicting amyloidosis. Other established and exploratory biomarkers (total tau, p-tau181, NRGN, YKL40, sTREM2, VILIP1 among other) show a wide range of correlation values depending on the fluid and the platform. Our results indicate that the multiplexed immunoassay platform produces reliable results for established biomarkers in CSF that are useful in research settings, with the advantage of measuring additional novel biomarkers using minimal sample volume.

Authors & Affiliations

Laura Ibanez1,2,3*#, Menghan Liu1,3#, Aleksandra Beric1,3#, Jigyasha Timsina1,3, Pat Kholfeld1,3,
Kristy Bergmann1,3, Joey Lowery1,3, Nick Sykora1,3, Brenda Sanchez-Montejo1,3, Will Brock1,3,
John P. Budde1,3, Randall J. Bateman2,4,5,6, Nicolas Barthelemy2,5, Suzanne E. Schindler2,4,6, David M Holtzman2,4,6, Tammie L. S. Benzinger7,4,6, Chengjie Xiong8, Rawan Tarawneh9, Krista Moulder2,6, John C. Morris2,6, Yun Ju Sung1,3, Carlos Cruchaga1,2,3,4,6,10*

Department of Psychiatry, Washington University School of Medicine
Department of Neurology, Washington University School of Medicine
NeuroGenomics and Informatics Center, Washington University School of Medicine
Hope Center for Neurologic Diseases, Washington University School of Medicine
The Tracy Family SILQ Center, Washington University School of Medicine
Knight Alzheimer Disease Research Center, Washington University School of Medicine
Department of Radiology, Washington University School of Medicine
Division of Biostatistics, Washington University School of Medicine
Department of Neurology, University of New Mexico School of Medicine
Department of Genetics, Washington University School of Medicine

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.