Neurology Central

Unique tau filament structures discovered in head-injury associated dementia

Researchers from Medical Research Council (MRC; London, UK) have discovered the atomic structures of abnormal tau filaments related to chronic traumatic encephalopathy (CTE). The team also found that these tau structures are different from those found in Alzheimer’s disease.

Two years ago, the research team discovered the atomic structures of the tau filaments which contribute to Alzheimer’s disease, for the first time. Similar to Alzheimer’s, CTE is also associated with the abnormal build-up of tau protein in the brain, meaning the team was able to use the same technique to determine the unique structure of tau filaments in CTE.

In the study, published in Nature, the team removed tau filaments from the brains of three individuals with CTE post-mortem, before using cryo-electron microscopy facilities at the laboratory of molecular biology to image the tau filaments. The three individuals with CTE were found to have identical tau structures that were noticeably different to the tau structures seen in Alzheimer’s.

A remarkable variance between the tau filaments of Alzheimer’s and CTE was the formation of cavities in the CTE filaments, which were filled with other molecules.

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“We don’t know the chemical nature of these molecules yet, but we suspect they may play a role in the assembly of tau into filaments, and that their abundance may determine why some individuals develop CTE and others do not. The next stage of our research will be to identify these molecules and understand more about their role in tau assembly, as they may represent a possible target for drug development,” explained Sjors Scheres (MRC).

Michel Goedert (MRC) added: “The fact that the structures of the tau filaments were identical in the American football player and both boxers suggests that we’ve found a new criterion for post-mortem diagnosis of the disease. Our new knowledge of these structures could make it possible to diagnose CTE in living patients by developing tracer compounds that will specifically bind to the tau filaments of CTE.”

Results from the study could help to improve diagnosis and lead to the development of new treatments to prevent CTE disease progression. Joanna Latimer (MRC) concluded: “This new work builds on our knowledge of dementia and how different forms of the disease develop in the brain. Further understanding of how and why tau assembles into disease-specific folds will be crucial in the development of new treatments for CTE and other neurodegenerative diseases which involve defective tau.”

Sources: Falcon B, Zivanoc J, Zhang W et al. Novel tau filament fold in chornic traumatic encephalopathy encloses hydrophobic molecules. Nature doi:10.1038/s41586-019-1026-5 (2019) (Epub ahead of print);