PT  - JOURNAL ARTICLE
AU  - Xinyu Xiang
AU  - Tamta Arakhamia
AU  - Yari Carlomagno
AU  - Shikhar Dhingra
AU  - Manon Thierry
AU  - Michael DeTure
AU  - Casey N. Cook
AU  - Dennis W. Dickson
AU  - Leonard Petrucelli
AU  - Anthony W. P. Fitzpatrick
TI  - Role of molecular polymorphism in defining tau filament structures in neurodegenerative diseases
AID  - 10.1101/2021.05.24.445353
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.24.445353
4099  - http://biorxiv.org/content/early/2021/05/25/2021.05.24.445353.short
4100  - http://biorxiv.org/content/early/2021/05/25/2021.05.24.445353.full
AB  - Misfolding and aggregation of tau protein is implicated in many neurodegenerative diseases that are typified by the presence of large, filamentous tau inclusions. The aggregation of tau in human brain is disease-specific with characteristic filaments defining the neuropathology. An understanding of how identical tau isoforms aggregate into disparate filament morphologies in phenotypically distinct tau-related diseases remains elusive. Here, we determine the structure of a brain-derived twisted tau filament in progressive supranuclear palsy and compare it to a dissimilar tau fold found in corticobasal degeneration. While the tau filament core in both diseases is comprised of residues 274 to 380, molecular-level polymorphism exists. Potential origins of the molecular polymorphism, such as noncovalent cofactor binding, are identified and predicted to modulate tau filament structures in the brain.Competing Interest StatementThe authors have declared no competing interest.