The atomic structures of the abnormal tau filaments associated with chronic traumatic encephalopathy (CTE), a head injury-associated neurodegenerative disease, are investigated in new research from the MRC Laboratory of Molecular Biology (LMB). The work found that the filaments differ in structure from those seen in Alzheimer’s disease.
The findings could lead to improved diagnosis of CTE, which is often not made until after death, and the development of new treatments to prevent its progression.
CTE is associated with repeated blows to the head, particularly in relation to contact sports, such as boxing, rugby and football. The symptoms of CTE include behavioural changes, confusion and memory loss.
The exact causes of the disease are not fully understood however, and it is not known why only some people exposed to repeated head injury appear to develop the disease. The condition was first described in the 1920s and was known as ‘punch drunk syndrome,’ and later dementia pugilistica, because some ex-boxers developed dementia.
Two years ago, the same group of scientists at the LMB revealed for the first time the atomic structures of the tau filaments which lead to Alzheimer’s disease.
[caption id=“attachment_98573” align=“aligncenter” width=“680”] A cross section of the type-I CTE filament.
CTE, like Alzheimer’s, is associated with the abnormal build-up of tau protein in the brain. This study used the same technique to discover that CTE has its own unique structure of tau filaments.
CTE Tau Filaments
The researchers extracted tau filaments from the brains of three individuals with CTE post-mortem: one former professional American football player and two former professional boxers. The filaments were then imaged using the cryo-electron microscopy facilities at the LMB, Diamond Light Source and the University of Leicester. The team found identical tau structures from the three patients with CTE that were different from those seen in Alzheimer’s.
One striking difference between the CTE and the Alzheimer filaments was the formation of cavities in the CTE filaments, which are filled with other molecules.
“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,"
said Sjors Scheres, a research leader at the MRC LMB and lead author of the study.
Benjamin Falcon, Jasenko Zivanov, Wenjuan Zhang, Alexey G. Murzin, Holly J. Garringer, Ruben Vidal, R. Anthony Crowther, Kathy L. Newell, Bernardino Ghetti, Michel Goedert & Sjors H. W. Scheres Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules Nature (2019). DOI: 10.1038/s41586-019-1026-5
Top Image: UC Berkeley