Tracing the origins of tau in blood
Developing CNS- and PNS-specific tau biomarkers to distinguish brain-derived tau from peripheral tau and improve disease monitoring.
The problem
What's the challenge, and why is it so hard to solve?
Tau is widely used as a blood biomarker for Alzheimer's disease and other neurodegenerative disorders. However, tau is produced not only in the brain but also in the peripheral tissues. While the central nervous system (CNS) primarily expresses low-molecular-weight tau, peripheral nerves express a distinct form known as Big Tau. While emerging brain-derived BD-tau biomarkers provide greater specificity for brain pathology, we still know little about how peripheral tissues contribute to circulating tau.
Our approach
How are we tackling the challenge?
We are building a comprehensive map of tau across human tissues to understand how different tau forms are distributed throughout the body. Using a recombinant isotopically labeled tau standard and targeted mass spectrometry, we quantify tissue-specific tau proteoforms generated by alternative splicing in the brain, peripheral nerves, and other tissues. We then translate these tissue-specific tau signatures into blood-based biomarkers to address a fundamental question: where does circulating tau come from?
Why it matters
What difference could this make for patients and society?
Because CNS- and PNS-derived tau both circulate in blood, each can confound measurement of the other. By distinguishing central nervous system (CNS) and peripheral nervous system (PNS) sources of tau, we aim to improve biomarker interpretation, enhance diagnostic accuracy, and develop new tools for both neurodegenerative and peripheral nerve disorders.
Potential benefits include:
- More specific measurement of CNS neurodegeneration
- Improved performance of p-tau biomarkers in individuals with comorbid conditions
- Better understanding of tau biology across tissues
- New blood biomarkers for peripheral neuropathies and other nerve disorders
What's next
Once we've solved this, what do we want to explore next?
We are validating CNS- and PNS-specific tau assays in neurodegenerative diseases, traumatic nervous system injuries, and peripheral neuropathies. Our goal is to establish the next generation of tissue-specific tau biomarkers that improve disease detection, monitoring, and biological understanding across both central and peripheral nervous system disorders.
Key publications
Where can I read more?
Team
Who's working on this?