In this episode, Professor Louise Serpell is joined by 2026 Rainwater Prize winners Professor Dennis Dickson, Professor Melissa Murray and Dr Marc Busche.

They talk about their work and the science that led to them earning this much deserved award, reflecting on decades of research into tau and its role in neurodegenerative disease. The conversation explores how tau functions in the healthy brain, how it becomes harmful in conditions such as Alzheimer’s disease and progressive supranuclear palsy, and why certain brain regions are especially vulnerable.

The discussion covers different forms of tau, including soluble species that may disrupt how neurons fire before visible tangles appear. Brain banking, imaging and fluid biomarkers are highlighted as key tools for understanding disease differences and improving diagnosis. The importance of rare MAPT mutations and what they can teach us about future treatments is also explored.

Alongside the science, there are thoughtful reflections on mentorship, risk taking and the value of asking ambitious questions in dementia research.

Key Takeaways

• Tau is essential but context dependent. It is vital for normal brain function, yet changes in its chemistry, structure or location can drive neurodegeneration.
• Tangles are not the whole story. Soluble tau species can disrupt neuronal firing, even in single cells, before visible aggregates appear.
• Selective vulnerability defines tauopathies. Disorders such as PSP consistently affect specific brain regions & cell types, including glia, & we do not fully understand why.
• One biomarker does not fit all. Tau PET and fluid markers behave differently across Alzheimer’s disease and primary tauopathies, reflecting structural differences in tau.
• Progress depends on bold science. High risk experiments, strong mentorship and access to the right tools are essential for moving the field forward.

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