University of Pittsburgh researchers have developed a novel biofluid biomarker to identify early-stage pre-tangle tau aggregates. Using single molecule array (Simoa®) technology, an ultrasensitive assay for early-stage soluble tau aggregates (STAs) has been developed and validated. This novel assay could assist in earlier diagnosis of Alzheimer’s disease (AD) ensuring early treatment or in the development of treatments targeting STAs, resulting in better outcomes for patients with AD and their loved ones.
A novel CSF assay has been developed that can detect the presence of STAs prior to the formation of NFTs and onset of the cognitive symptoms of AD. STAs could be useful biomarkers for the early stages of AD and act as a useful therapeutic target to prevent the formation of NFTs.
Description
AD, a neurogenerative disease that affects at least 30 million people worldwide, impacts the health and quality of life of the patient and has a devastating impact on loved ones and caregivers. A defining feature of AD is the presence of fibrillar intracellular aggregates of polymerized tau proteins, with the severity of pathology in insoluble tau neurofibrillary tangles (NFTs) correlating to cognitive decline. Treatment of AD patients with little or no quantifiable NFTs has been much more clinically beneficial than treatment of more advanced NFTs and preventing NFT formation is a promising therapeutic approach. NFTs are assembled using early-stage STAs. The assay could identify STAs from cerebrospinal fluid (CSF) before NFTs are detectible allowing for early detection and treatment of AD. Additionally, STAs could act as therapeutic targets for novel treatments or as biomarkers of efficacy in research studies. This novel, ultrasensitive assay has the potential to revolutionize treatment and diagnostic options in patients with AD and other tauopathies.
Applications
• Alzheimer’s disease
• Tauopathy diseases
Advantages
Currently, AD is clinically diagnosed in living patients by positron emission tomography (PET) imaging of brain tau aggregates. PET cannot detect early-stage STAs prior to the formation of NFTs and there is a pressing clinical need for a biomarker for early-stage tau formation. This novel assay can identify STAs from CSF and could be an early diagnostic and prognostics biomarker for AD. STAs could be therapeutic targets, and this assay would allow for discovery of agents to target STAs in AD. Additionally this assay can also distinguish between AD and non-AD tauopathies and could aid diagnosis of other conditions by eliminating AD during differential diagnosis.
Invention Readiness
A three-step Simoa® assay to detect STAs in human CSF was developed and validated using antemortem CSF samples paired with postmortem neuropathological diagnosis and PET studies. An inverse relationship was discovered between CSF levels of STAs and severity of Braak NFT stages (a measure of AD brain pathology). CSF STAs positively correlated with three different clinical measures of cognitive performance, all highlighting the potential for STAs to be used a biomarker in AD.
IP Status
https://patents.google.com/patent/WO2026033422A1Related Publication(s)
Islam, T., Hill, E., Abrahamson, E. E., Servaes, S., Smirnov, D. S., Zeng, X., Sehrawat, A., Chen, Y., Kac, P. R., Kvartsberg, H., Olsson, M., Sjons, E., Gonzalez-Ortiz, F., Therriault, J., Tissot, C., Del Popolo, I., Rahmouni, N., Richardson, A., Mitchell, V., … Karikari, T. K. (2025). Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer’s disease. Nature Medicine, 31(2), 574–588. https://doi.org/10.1038/s41591-024-03400-0
