Tautrace™: an ultrasensitive immunoassay for neurodegenerative protein biomarkers

Award Details: The National Institute on Aging (Aging Research program, CFDA 93.866) awarded Adeptrix Corp a Project Grant of $499,940 on September 11, 2025, with an ultimate completion date of August 31, 2026. The award supports research and development conducted in Massachusetts.

Products and Services: Adeptrix is developing TAUTRACE, an ultrasensitive immunoassay platform designed to detect and quantify phosphorylated tau (pTau) biomarkers in cerebrospinal fluid and plasma at femtogram/milliliter concentrations. The platform employs lanthanide-labeled antibodies and secondary ion mass spectrometry (SIMS) detection to identify distinct molecular forms of tau protein, including full-length and proteolytically cleaved variants, which serve as critical biomarkers for Alzheimer's disease diagnosis and therapeutic response evaluation. By enabling simultaneous detection of multiple non-overlapping epitopes on tau targets, TAUTRACE addresses a significant unmet clinical need for minimally invasive liquid biopsy solutions that can generate relative abundance profiles of multiple tau proteoforms. The resulting analytical platform is intended to provide clinicians and researchers with a simple, robust, and cost-effective tool for in-house discovery applications that support personalized Alzheimer's disease diagnostics and companion diagnostics.

Abstract

Alzheimer's disease (ad) is a devastating neurodegenerative disorder characterized by the formation of neurofibrillary tangles composed of hyperphosphorylated TAU protein. Cerebrospinal fluid (CSF) and plasma levels of phosphorylated TAU (ptau), are critical biomarkers used in molecular tests for diagnosing alzheimer's disease (ad), with TAU phosphorylated at the THR217 site (PTAU217) showing a strong correlation with the formation of ad-specific TAU tangles in the brain. However, current analytical methods lack the sensitivity required to detect and quantify the extremely low abundant disease-specific TAU proteoforms present in biofluids at femtogram/milliliter (FG/ML) concentrations. This major unmet need hinders the development of personalized ad diagnostics and companion diagnostics for evaluating therapeutic response. To address this need, adeptrix proposes to develop tautrace™, a novel ultrasensitive immunoassay platform capable of quantifying distinct molecular forms of TAU in CSF and plasma down to FG/ML levels. Tautrace™ is based on a sandwich immunoassay format using lanthanide-labeled antibodies and secondary ION mass spectrometry (sims) detection. This technology enables the detection of single ions, allowing for the quantification of distinct molecular forms of TAU in minimally invasive blood samples. A key innovation of tautrace™ is its ability to independently probe multiple sites within a protein target by simultaneously applying several detection antibodies that recognize non-overlapping epitopes. This unique feature distinguishes IT from other high sensitivity immunoassays and allows for the generation of relative abundance profiles of multiple TAU proteoforms, such as differentiating between full-length TAU and proteolytically cleaved forms. The liquid biopsy platform offers a simple, robust, and affordable solution for customers to perform in-house discovery and validation of low-abundance biomarkers, reducing reliance on specialized service providers. In this phase i study, we will establish feasibility by developing lanthanide-tagged antibody probes against total TAU (ttau) and PTAU217, and validating their performance in quantifying these analytes in human CSF and plasma samples. Milestones for this project include achieving minimum signal-to-noise ratios for detecting ttau and PTAU217 in CSF and plasma, as well as measuring the ttau/PTAU217 ratio with a coefficient of variation of less than 15% in replicate assays. Successful completion will enable further development of tautrace™ in a phase II proposal into a comprehensive, affordable liquid biopsy platform for multiplexed quantification of low abundance TAU proteoforms and other neurodegenerative biomarkers to support early ad diagnosis, disease monitoring, and therapeutic development.