Pressing tau research questions the Nautilus Voyager™ Platform can help answer

The tau protein is deeply associated with the progression of Alzheimer’s disease and related dementias. By studying it at the proteoform level, we firmly believe researchers will discover the mechanisms of neurodegeneration. In our recent preprint as well as our US HUPO 2026 seminar, you’ll find some brief examples of how the Nautilus Voyager™ Platform is already revealing novel insights into tau biology. Studies like these will hopefully drive the development of new means to fight neurodegenerative disease.

While we’re already making great progress, we cannot wait for more researchers to begin exploring biology with the platform. You can be one of the first to use the Nautilus Tau Proteoforms Assay through participation in the Iterative Mapping Early Access Program. Below we share some of the questions the assay may help answer. This is far from an exhaustive list, and we strongly encourage you to submit your project ideas through the Early Access Program.

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What tau proteoforms are present during each stage of Alzheimer’s disease?

Alzheimer’s disease is currently diagnosed post-mortem or through positron emission tomography and the measurement of blood or cerebrospinal fluid biomarkers (Jack Jr. et al., 2024). These diagnostic methods look for evidence of amyloid plaques and tau tangles in the brain. They can be used to stage patients as it is known that amyloid beta plaques form first followed by tau-based neurofibrillary tangles (NFTs) and progressive neurodegeneration with NFTs spreading to new brain regions. Importantly, while Alzheimer’s generally follows this “biological staging,” patients at different biological stages can differ widely in their levels of cognitive decline and there may be different forms of tau and/or amyloid beta present at each stage or associated with different levels of decline.

By identifying the forms of tau associated with different biological and cognitive stages of Alzheimer’s disease, researchers may be able to develop better treatments for those stages. For instance, some tau proteoforms may only be present at certain biological stages making it impossible to treat those stages with drugs targeting proteoforms uniquely present at other stages. Furthermore, there may be specific tau proteoforms associated with cognitive decline at different biological stages. Understanding how tau proteoforms intersect with biological stages and levels of cognitive decline may be crucial for treating and preventing Alzheimer’s disease.

Are there distinct tau proteoforms in distinct tauopathies?

Tau pathology is associated with a wide variety of neurodegenerative diseases commonly called “tauopathies.” These have different clinical courses, effects on brain regions, and impacts on the proteome. Attempting to treat all of them the same way may lead to adverse outcomes.

Understanding what treatments are best for which patients begins with understanding what tauopathies they actually have. By quantifying the tau proteoforms present in different tauopathies, researchers may identify specific proteoform profiles indicative of different diseases. Later researchers may develop these profiles into clinical biomarkers used to differentiate among tauopathies and guide treatment. Specific proteoforms may even become useful drug targets in specific diseases.

What tau proteoforms give rise to tau seeds and aggregates?

Pathogenic tau can come in the form of seeds, oligomers, or fibrils. These may all comprise different proteoforms and knowing what tau proteoforms are found in each may be key to giving patients the best treatments. For instance, a person with early-stage Alzheimer’s disease in which tau has not yet aggregated may benefit from drugs targeting tau seed precursors. Alternatively, a patient who already has tau seeding might benefit from therapies designed to prevent spread through oligomers. Finally, in a person with late-stage Alzheimer’s, it may be best to target proteoforms from all three species to both get rid of the fibrils and prevent the creation of new ones. Identifying the proteoforms underlying seeds, oligomers, and fibrils is the first step in learning how to target them.

What tau proteoforms do other proteins interact with?

Alzheimer’s disease and related dementias are associated with many more proteins than tau or amyloid beta. If there is a protein that’s known to play a key role in one of these conditions, but it is not targetable for some reason, it may be beneficial to learn what tau proteoforms this protein interacts with to achieve its detrimental effects. In this way, those proteoforms could become proxy drug targets. The opposite is possible as well – if a tau proteoform is not targetable, but one of the proteins it interacts with is, that other protein may be a good drug target. The Nautilus Voyager™ Platform provides reserachers with the unique opportunity to study tau proteoform interactions with single-molecule resolution.

Join the Iterative Mapping Early Access Program and bring single-molecule proteomics in your workflows

These are just a few of the many questions about tau that researchers can answer with the Nautilus Voyager™ Platform. We will be expanding the platform’s capabilities with additional proteoform targets as well as broadscale proteomics applications in the coming months. If you’d like to be one of the first to incorporate the platform into your workflows, please submit a project idea through the Iterative Mapping Early Access Program. We cannot wait to see what questions you use the platform to answer.