• Studies will investigate progressive supranuclear palsy, corticobasal degeneration and other pathologies driven by tau.
• One study will explore if tau biological activity and structure vary based on its source.

The Rainwater Charitable Foundation has awarded $3 million in grants to fund four investigators in its 2026 Tauopathy Challenge Workshop.

These researchers will explore the molecular mechanisms of tau pathology, with implications for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Alzheimer’s disease and other neurodegenerative disorders characterized by abnormal tau protein accumulation.

The Alzheimer’s Association, the Aging Mind Foundation and CurePSP are collaborating with the Rainwater Charitable Foundation to support the awards.

Healio spoke with Glenn Harris, PhD, director of research partnerships, business development and drug discovery at Rainwater, as well as with grant recipient Edward B. Lee, MD, PhD, director of the Center for Neurodegenerative Disease Research at the Perelman School of Medicine, to find out more.

Healio: What are the goals of the 2026 Tauopathy Challenge Workshop?

Harris: The Tauopathy Challenge Workshop is designed to tackle difficult, unresolved questions in tau science by bringing together researchers with different areas of expertise to develop new approaches. Each year, we focus on a specific scientific challenge, with funding available to advance the most promising ideas that emerge.

For 2026, the workshop focused on the structural and thermodynamic properties of tau protein and its interactions with other pathologies. This is an area with important implications for understanding how tau adopts different conformations, how it aggregates and how it contributes to neurodegeneration. We ultimately selected four projects for a combined $3 million in funding, with the goal of generating insights that can inform future biomarkers, diagnostics and therapeutic strategies.

Healio: Specifically, why is tau an important focus of research in neurodegenerative diseases?

Harris: Tau is implicated across a broad spectrum of neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy and corticobasal degeneration. Normally, tau is a microtubule-associated protein that plays an important role in maintaining neuronal structure and function. In disease, alterations in tau may promote misfolding, aggregation and the formation of pathological deposits associated with neuronal dysfunction and degeneration.

One of the major challenges is that tau pathology is remarkably heterogeneous. Tau can adopt different conformations, undergo different post-translational modifications and accumulate in different cell types and brain regions. We still have important questions about which of those differences drive toxicity, which are most relevant to disease progression, and where there may be opportunities to intervene.

That makes tau integral not only as a defining feature of several neurodegenerative diseases, but as a potential source of biomarkers and therapeutic targets. Improving our understanding of tau biology could have implications across multiple diseases in which tau pathology contributes to neurodegeneration.

Healio: Why is this an exciting time for tau research?

Lee: Recent advances in cryo-electron microscopy and other molecular technologies are allowing researchers to study disease-associated proteins directly from human brain tissue at near-atomic resolution. These breakthroughs are giving us an unprecedented view of the structures that underlie neurodegenerative diseases and creating new opportunities to develop targeted therapies.

Healio: What can you tell us about PSP and CBD and why they are included in the challenge?

Harris: PSP and CBD are rare, progressive neurodegenerative diseases with substantial unmet clinical need. Both can affect movement, cognition and other neurologic functions, and neither currently has a disease-modifying treatment.

They are also primary tauopathies, which makes them particularly valuable scientifically. In Alzheimer’s disease and many other neurodegenerative conditions, multiple pathologies are present simultaneously. In PSP and CBD, tau is the predominant pathology, giving researchers an opportunity to examine its relationship to neurodegeneration more directly.

Primary tauopathies like PSP and CBD can serve as important pathfinders for the broader field. Because tau is the predominant pathology, they offer an opportunity to investigate fundamental questions about how tau pathology develops, why certain cells and brain regions are particularly vulnerable and which mechanisms may offer promising points for therapeutic intervention. What we learn can deepen our understanding of PSP and CBD while also providing insights relevant to other neurodegenerative diseases.

Lee: Progressive supranuclear palsy and corticobasal degeneration are both neurodegenerative diseases characterized by the accumulation of abnormal tau protein in brain cells. They can cause problems with movement, balance, cognition, and behavior. Although both are considered tauopathies, they affect different brain regions and cell types, suggesting that distinct forms of tau pathology may contribute to their unique clinical features.

Healio: Dr. Lee, you received $750,000 for your study of the role of tau in PSP. What prompted this study, and what do you hope to uncover?

Lee: PSP is a devastating tau-related neurodegenerative disease, but we still do not fully understand why tau pathology develops differently across the various cell types in the brain. Our preliminary findings suggest that tau from astrocytes and oligodendrocytes may behave differently from tau in neurons. We hope to determine whether tau’s biological activity and structure vary depending on the cell it comes from, which could fundamentally change how we think about disease mechanisms in PSP.

Healio: What role will new technologies play in your study?

Lee: This project combines several cutting-edge technologies, including fluorescence-activated cell sorting, laser capture microdissection, and advanced cryo-electron microscopy. These tools allow us to isolate tau from specific brain cell types and visualize its structure at unprecedented resolution, bringing us closer to understanding how tau drives neurodegeneration in the human brain.

Healio: Three other researchers received awards in this program. Could you summarize what their studies will investigate and why this research is significant?

Harris: Alongside Dr. Edward Lee’s work, the three other funded projects approach the broader challenge of tau biology from different but complementary angles.

Carlo Condello, PhD, at the University of California, San Francisco, is investigating whether tau adopts distinct molecular conformations in different cell types in PSP and CBD, including neurons and glial cells. That work could help us better understand how cell-specific forms of tau contribute to disease and whether those differences could eventually inform more precise biomarkers or therapeutic approaches.

Daniel C. Lee, PhD, at the University of Kentucky, is studying citrullination, an irreversible post-translational modification of tau, and how it interacts with phosphorylation. His work is exploring a relatively understudied aspect of tau biology that could provide new insight into the molecular changes that influence tau structure and aggregation.

Sue-Ann Mok, PhD, at the University of Alberta, is focused on the earliest stages of tau aggregation and the factors that influence whether pathological aggregates form or can be disrupted. Her work could help clarify some of the initial molecular events that set tau pathology in motion and potentially identify new points for therapeutic intervention.

Together with Dr. Edward Lee’s research examining tau within the cellular environment of human brain tissue, these studies give us an opportunity to look at tau across multiple levels of disease biology, from molecular modifications and early aggregation to cell-specific conformations and pathology in human tissue. That range is important because no single study can answer every question surrounding tau pathology. Each project adds a different piece to our understanding of what drives disease and where there may be opportunities to intervene.

Healio: What impact do you hope these studies will have on clinical care and outcomes?

Harris: The path from understanding disease biology to changing clinical care is rarely direct. The questions these investigators are asking sit upstream of several major clinical challenges in tauopathies.

An understanding of the molecular forms of tau, how they differ across cell types and disease states, and which biological changes accompany pathology could help direct us towards the discovery of more specific biomarkers. That could ultimately improve our ability to prudently identify and characterize disease, monitor progression, and select the right patients for clinical trials.

The same knowledge may also be translated towards therapeutic development. If we can identify which aspects of tau biology are driving toxicity, we can begin to define more precise targets for intervention. And a clearer understanding of disease mechanisms can help researchers design clinical trials around the biology a therapy is intended to affect.

These projects are addressing fundamental science, and that foundation is critical. Our long-term goal is to create a more precise understanding of tauopathies that can translate into better diagnostics, better-designed trials and, ultimately, effective disease-modifying therapies.

Lee: Our goal is to provide a more precise understanding of the toxic forms of tau that drive disease. If different cell types produce distinct pathogenic tau species, future therapies may need to target those forms specifically. Ultimately, we hope this work will help guide the development of more effective treatments for PSP and related tauopathies.

Healio: Do you have anything else you would like to add about this program?

Harris: One of the things we value most about the Tauopathy Challenge Workshop is that the funding is only one part of the program. Each year, we select a new challenge topic in tau science and deliberately gather multiple perspectives. The Workshop brings together researchers and gives them an opportunity to exchange ideas before the research projects are fully formed.

Convening researchers with different expertise into the same room can change the questions being asked and open approaches that might not emerge within a single discipline. Because we take on a different challenge each year, we can use that model to explore some of the neglected gaps in tau science with fresh perspectives.

We’re unbelievably fortunate to do this alongside the Alzheimer’s Association, Aging Mind Foundation and CurePSP. Their support allows us to put greater resources behind promising ideas and reflects a shared commitment to accelerating progress in tau-driven diseases.

Ultimately, we want the Workshop to do more than fund individual projects. We want it to generate new collaborations, bring original thinking into the field, and build knowledge that other researchers can use. We want the ideas and relationships that come out of the Workshop to continue shaping the science well beyond the projects we fund.

For more information:

Glenn Harris, PhD, and Edward B. Lee, MD, PhD, can be reached at neurology@healio.com.