Alzheimer’s disease (AD) is the most prevalent neurodegenerative condition in the United States, imposing a significant economic burden on society. Costs surpassed $345 billion in 2023 and are projected to reach $1 trillion by 2050, as reported by the Alzheimer’s Association. Early and accurate diagnosis of AD and related dementias (ADRD) is crucial for effective treatment. Biomarkers for ADRD not only aid in early diagnosis and treatment but also enhance drug discovery by enabling patient stratification and improving clinical trial success rates. On the therapeutic front, the repertoire of disease-modifying treatments for AD remains exceptionally limited. The development of such treatments is hindered by the absence of suitable biomarkers for monitoring their efficacy, along with challenges in objectively assessing target engagement during trials.
Given the important roles of Tau ubiquitination in the AD pathophysiology and disease progression, it is imperative to explore ubiquitinated Tau as a potential biomarker for AD. Currently, there are no blood-based Ub-Tau biomarker assays reported in the literature and adopted in the clinics. The PI’s lab has developed a patented method for generating well-defined and homogenous ubiquitinated Tau (Ub-Tau) that is crucial for the Single-Molecule Assay (Simoa) assay development and validation using a Quanterix SR-X Biomarker Detection System. Importantly our Ub-Tau species as a calibrator is crucial for the development of a quantitative assay. With this novel Ub-Tau Simoa assay, we will generate and optimize a novel Ub-Tau assay for the Quanterix SR-X system and compare the Ub-Tau concentration in plasma samples from 20 older adults with MCI vs. 20 age-matched unimpaired (healthy) controls (HC) to confirm that our assay is sensitive to detecting differences in Ub-Tau concentration based on clinically relevant phenotypes. This project will establish the validity of our assay for future research, diagnostic, and clinical applications.
