Excitement for Iterative Mapping of proteoforms at AAIC 2025
Nautilus Biotechnology
August 7, 2025
We just got back from AAIC 2025 where we met with many scientists in the Alzheimer’s disease research community. With our new preprint in hand, we shared how Iterative Mapping on the Nautilus Platform provides an entirely new way to do proteomics. Some of our key takeaways are found below. TLDR – AAIC attendees were very excited about the Nautilus Platform, and many would like to incorporate it into their research.
For more on the data we presented at AAIC 2025:
Alzheimer’s researchers need new ways to investigate tau
Researchers have known tau plays a role in Alzheimer’s disease for 50 years. Yet, only in the last year has knowledge of tau modifications advanced enough to incorporate them into advanced blood tests.
There is still much to learn about tau biology and the gaps in our knowledge make it difficult to:
- Distinguish among different diseases involving tau (tauopathies)
- Forecast disease progression
- Determine which forms of tau are pathogenic
- Target the pathogenic forms of tau with novel therapeutics
We’ll cover these topics in further detail below, but one overarching takeaway is that the conference highlighted the visceral and heart-wrenching impacts Alzheimer’s has on people’s lives, and Nautilytes were inspired by the passionate way this community is working to stop the suffering caused by Alzheimer’s and other neurodegenerative conditions.
The potential for tau biomarkers to distinguish between neurodegenerative diseases and forecast disease progression
There are many neurodegenerative diseases involving tau. These include Alzheimer’s disease, frontotemporal dementia, and progressive supranuclear palsy. Previous work suggests the tau proteoforms in these diseases are distinct. Thus, measuring tau proteoform profiles in these diseases may make it possible to precisely diagnose them and guide effective treatment.
Knowledge of tau proteoforms may also help researchers forecast disease progression. Researchers know that tau modifications increase as Alzheimer’s progresses. However, they don’t know what specific tau proteoforms are present at what quantities at different stages of disease. They also don’t know whether certain proteoforms potentiate the creation of others over the course of disease.
In our preprint, we present evidence suggesting there is an order underlying the creation of tau proteoforms and that certain proteoforms may potentiate the creation of others. By measuring tau proteoforms in large patient cohorts, researchers like those at AAIC may be able to unambiguously associate proteoform profiles with different stages of disease, identify which are the best predictors of disease severity/progression, and guide the development of new therapeutics.
Studying tau proteoforms to understand pathogenesis and develop new therapeutics
Attempts to target tau with therapeutic antibodies have failed in the past. As Nautilus Co-Founder and Chief Scientist Parag Mallick discussed in our most recent earnings call, researchers he met with at AAIC firmly believe we must understand tau’s proteoforms to understand it’s roles in biology and disease. Right now, we don’t know what forms of tau are involved in the mechanisms of neurodegeneration and tau aggregation. It’s entirely possible that previous tau-targeting clinical trials targeted the wrong tau proteoforms, and it may be necessary to target other proteoforms more specifically for substantial therapeutic impact.
Recent studies demonstrate different tau modifications have different disease trajectories, but for drug developers to choose the best targets, they must understand how these modifications relate to one another at the proteoform level. By examining proteoforms, researchers can determine how these modifications might potentiate each other, whether they’re shared among proteoforms found in healthy and cognitively impaired patients, and whether combinations of modification must be targeted for precise and effective therapeutic impacts.
Fostering new collaborations tapping into the power of Iterative Mapping
We are actively pursuing collaborations to utilize Iterative Mapping of proteoforms to explore new biology. We’re incredibly excited that the Allen Institute will be one of the first to use Iterative Mapping to investigate the connections between the tau protein and Alzheimer’s disease. Furthermore, AAIC attendees gave us very positive feedback on our recent data, and we continue to build relationships with many people we met at the conference. More than anything, our time at AAIC showed us that technologies like ours can help improve lives. We are confident that this entirely new way to do proteomics will lead to tremendous advances in how researchers understand disease, develop biomarkers, and identify drug targets for better therapeutic outcomes.
Reach out if you’d like to incorporate Iterative Mapping of proteoforms into your work
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