Scientists Advance Understanding of the Nature of Alzheimer’s Disease
20:48 12 October, 2026In neurodegenerative diseases such as Alzheimer’s disease, progressive neuronal damage is associated with the accumulation of abnormal tau filaments in the brain. The core of these tau filaments forms a highly ordered structure, while molecules such as ubiquitin attach to the tau protein around the core as post-translational modifications. However, the specific role of these peripheral modifications in maintaining the structural stability of tau filaments remains unclear.
In this study, published in Nature Structural & Molecular Biology, researchers from the University of Tsukuba isolated tau filaments from the brain tissue of patients with Alzheimer’s disease and vacuolar tauopathy, a rare inherited neurodegenerative disorder, Scientific Russia reports. They investigated the biological and structural properties of these filaments through experiments involving their inoculation into mice and analysis using cryo-electron microscopy.
Tau filaments obtained from the two diseases induced different patterns of tau pathology in the brains of mice. Cryo-electron microscopy also revealed marked structural differences between tau filaments associated with Alzheimer’s disease and those found in vacuolar tauopathy. In the latter, researchers identified five types of filaments. In addition, a shift in polyubiquitin altered the interface between two protofilaments in some tau filaments, resulting in structures that had not previously been observed.
These findings indicate that tau filament structure may be influenced not only by its highly ordered core but also by the post-translational modifications surrounding it. The results offer new insights into the mechanisms that regulate the formation and stabilization of disease-specific tau filament structures and may broaden our understanding of the structural diversity observed in tau-related neurodegenerative diseases.