Multivariate models using NULISAseq and plasma p-tau217 for staging Alzheimer’s disease

Product:

CNS Disease Panel 120, Inflammation Panel 250

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120, Inflammation Panel 250

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

INTRODUCTION

Plasma phospho-tau217 (p-tau217) has been shown to demonstrate equal performance to cerebrospinal fluid (CSF) to predict amyloid beta (Aβ) positivity. Although such high-performing plasma tests provide confirmatory information on Aβ status, further information is desperately needed to discern optimal blood-based biomarkers (BBMs) across the Alzheimer’s disease (AD) stage.

METHODS

From the Australian Imaging, Biomarkers and Lifestyle study, 387 participants underwent [¹⁸F]NAV4694 (Aβ) and [¹⁸F]MK-6240 (tau) PET scans, a blood test to measure for p-tau217 (ALZpath and Lumipulse), and the Alamar Biosciences NULISASeq platform (120 central nervous system [CNS] and 250 inflammatory proteins). Individual p-tau217 assays were compared with selected biomarker sets from the Alamar panel to predict AD stage.

RESULTS

Using a panel of biomarkers was significantly better at predicting disease stage compared with p-tau217 alone; however, the difference was dependent upon p-tau217 assay.

DISCUSSION

Utility of extra BBMs in addition to p-tau217 provides useful information regarding overall disease burden during the separate stages of AD.

Highlights

Of the separate assays for p-tau217, the Lumipulse assay demonstrated significantly better performance than the ALZpath assay to separate disease stages.
Multivariate blood-based biomarker (BBM) models are significantly better at predicting the presence of A/T from A–T– as compared with any p-tau217 assay.
Multivariate BBM models have higher area under the curve values to predict disease stage than Alamar and ALZpath p-tau217, but not Lumipulse p-tau217 during later disease stage comparisons.

Authors & Affiliations

James D. Doecke¹, Edwin Stage², Christopher Fowler³, Vincent Doré⁴⁵, Nils Boehm⁶, Christoph Kleinert⁶, Malleswari Challagundla⁶, Azadeh Feizpour³⁴, Larry Ward³, Jurgen Fripp¹, Colin L. Masters³, Christopher Rowe³⁴, Anthony Bannon²

¹ Australian E-Health Research Centre, CSIRO, Herston, Queensland, Australia
² AbbVie, North Chicago, Illinois, USA
³ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
⁴ Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, Australia
⁵ Australian E-Health Research Centre, CSIRO, Parkville, Victoria, Australia
⁶ Quantitative, Translational and ADME Sciences, Biomarker Bioanalysis, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen am Rhein, Germany

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.