The Alzheimer’s Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study

Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

INTRODUCTION

The Alzheimer’s Association Global Biomarker Standardization Consortium conducted a blinded case–control study to learn which phosphorylated tau (p-tau) assays provide the largest fold-changes in Alzheimer’s disease (AD) versus non-AD and show commutability in measuring patient samples and candidate certified reference materials (CRMs).

METHODS

Thirty-three different p-tau assays measured paired plasma and cerebrospinal fluid (CSF) from 40 participants (25 with “AD pathology” and 15 with “non-AD pathology” by CSF amyloid beta [Aβ]42/Aβ40 and p-tau181 criteria). Four CRMs were assessed.

RESULTS

Plasma p-tau217 demonstrated higher fold-changes between AD and non-AD than other p-tau epitopes. Fujirebio LUMIPULSE G, UGOT IPMS, and Lilly MSD p-tau217 provided the highest fold-changes. Plasma p-tau217 showed the strongest correlations between plasma assays (rho = 0.81–0.97). The CRMs were not commutable across assays.

DISCUSSION

Plasma p-tau217 showed larger fold-changes and better accuracy for detecting AD pathology in symptomatic individuals, with greater cross-platform agreement than other p-tau variants. Further work is needed to develop suitable CRMs facilitating cross-assay standardization.

Highlights

  • Paired plasma and cerebrospinal fluid (CSF) samples from twenty-five Alzheimer’s disease (AD) and 15 non-AD patients were measured blind.
  • Thirty-three plasma assays were compared, for phosphorylated tau-181 (p-tau181), 205, 212, 217 and 231.
  • Plasma p-tau217 consistently had the highest fold-change and was best correlated between assays.
  • Plasma-CSF correlations were weak to moderate.
  • There was lack of commutability for four candidate reference materials.

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.