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Highly sensitive multiplexed detection of brain-derived Tau and phosphorylated Tau proteoforms with the NULISA technology

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  • July 28, 2025
Topic/Product:
AQ, Immunology, Inflammation
Disease Area:
Sample Type:

Abstract

Background: Blood-based biomarkers hold great promise for the early detection and management of Alzheimer’s Disease (AD). While plasma Aβ42/Aβ40 ratios and phosphorylated Tau forms (pTau-181, pTau-217 and pTau-231) especially pTau-217 have shown high diagnostic accuracies to identify abnormal Abeta pathology, brain-derived Tau (BD-Tau), a brain-specific isoform of Tau, has demonstrated great promise as a blood-based biomarker for distinguishing AD from non-AD dementias and for predicting neurodegeneration. To address the need to measure BD-Tau and other Tau forms in plasma in a single multiplex assay to evaluate their diagnostic performance and clinical utility, we sought to develop an ultrasensitive BD-Tau assay with the novel Nucleic-acid Linked Immuno-Sandwich Assay (NULISA) technology. Incorporation of the BD-Tau assay into the NULISAseq CNS Disease Panel 120 enables simultaneous profiling of multiple Tau proteoforms along with other important AD biomarkers in a single assay.

Methods: We developed a NULISA BD-Tau assay by pairing a monoclonal antibody targeting MAPT exon 4-5 junction with an antibody detecting total-Tau (t-Tau). Detectability for BD-Tau was evaluated in 100 plasma samples with the NULISA Single-plex assay. Integration of BD-Tau into the CNS Disease Panel 120, a multiplex panel for detection of ~120 key markers of neurodegeneration, inflammation and synaptic pathology, was assessed for interference with other Tau isoforms. Additionally, correlations were performed with t-Tau assays in both plasma and
CSF samples with single-plex and multiplex readouts.

Results: The NULISA BD-Tau assay provides highly specific detection of BD-Tau with 100% quantifiability in both plasma and CSF (n=86 each). As expected, BD-Tau measurements showed very high correlation with t-Tau in CSF samples (R=0.99), and lower correlation in plasma likely due to the presence of both peripheral and CNS-derived Tau forms in blood. Addition of BD-Tau to the CNS Disease Panel 120 showed minimal interference for detection of existing Tau forms (total Tau, t-pTau-181, t-pTau-217 and t-pTau-231) in plasma (n=86).

Conclusion: The NULISA BD-Tau assay and its integration into the 120-plex NULISAseq CNS Disease Panel 120 provide powerful tools to develop blood-based biomarkers for AD and enable deeper insights into AD pathogenesis and progression.

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Authors & Affiliations

Xiao-Jun Ma1*, Shweta Iyengar1, Shalaka Deshmukh1, Roopa Comandor1, Li Wang1, Sean Kim1, Xiaomei Xu1, Wei Feng1, Xiaolei Qiu1, Bingqing Zhang1, Yuling Luo1

1Alamar Biosciences Inc., Fremont, California, USA

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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.

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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.