Publications

HAI 2026 – Development of a Highly Sensitive and Automated Immunoassay for Brain-Derived pTau-217: Analytical Performance in Human Plasma Samples

Product:

Alzheimer's, pTau

Topic:

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Topic/Product:

Alzheimer's, pTau

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

Background: Blood-based biomarkers are increasingly recognized as valuable tools for early detection and longitudinal monitoring of Alzheimer’s Disease (AD). Among these, plasma pTau-217 demonstrates high discriminative accuracy for amyloid-PET positivity. However, most circulating pTau-217 originates from peripheral sources, with only ~20% derived from the brain. This highlights the need for a highly sensitive and specific assay to detect brain-derived (BD) pTau-217, a brain-specific isoform that more accurately reflects AD neuropathology.

Methods: We previously developed a novel proximity ligation-based NULISA technology, which integrates background suppression steps to enable attomolar sensitivity and automated protein detection across diverse biofluids1. Building on our prior development of a 120-plex NULISAseq CNS Disease Panel that enables relative quantification of BD-phosphorylated Tau isoforms along with other markers related to neurodegeneration and inflammation, we have developed a singleplex NULISA assay for absolute quantification of BD-pTau217 with high specificity and sensitivity. The assay was rigorously evaluated for key analytical parameters including dilution linearity, spike recovery, parallelism, accuracy, precision, reproducibility, and specificity.

Results: Our novel BD-pTau217 singleplex assay demonstrated strong analytical performance, with inter-plate CVs consistently below 20% across multiple operators, ARGO HT instruments, and days. The assay features a broad dynamic range (0.4–14,655 pg/mL) and a limit of detection of 0.08 pg/mL. In plasma samples from both healthy individuals and AD patients, overall BD-pTau217 detectability was over 95%. Characterization studies such as dilutional linearity, parallelism, and spike recovery confirmed robust assay performance. Additionally, the BD-pTau217 antibody exhibited minimal cross-reactivity with other Tau species, including total Tau, pTau181, pTau205, and pTau212, confirming its high specificity.

Conclusions: The NULISA BD-pTau217 singleplex assay represents a significant advance in blood-based biomarkers for AD, providing brain specificity without the need for cerebrospinal fluid.

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.