A mystery molecule may help diagnose chronic traumatic encephalopathy

Researchers have discovered an unusual folding pattern around an unknown hydrophobic molecule in the tau protein in the brains of a football player and two boxers who had chronic traumatic encephalopathy (CTE). The team, led by Michel Goedert and Sjors H. W. Scheres of the MRC Laboratory of Molecular Biology, used different types of cryo-electron microscopy to determine that the protein folds and aggregates in distinct helical patterns, different from what is found in other neurodegenerative diseases, around a hydrophobic moiety (Nature 2019, DOI: 10.1038/s41586-019-1026-5). Based on the location of the tau tangles, the researchers think the hydrophobic molecule may leak out of the blood during the repeat head trauma and inflammation that causes CTE. However, they don’t know what it is. Scheres suspects it may be a steroid or a fatty acid. The race is now on to identify the hydrophobic molecule and to find compounds that might displace it or destabilize tau folding or aggregation. Scheres also thinks the folding pattern will be detectable using imaging methods. Today, CTE can be conclusively diagnosed and studied only after someone has died.