Tau Fragments and PHFs

TauRx workers first discovered that tau protein is the main constituent of the tangle filaments (paired helical filaments, PHFs) that form in Alzheimer’s disease back in 1988 (Wischik et al., 1988, PNAS 85:4884-4888). At the time they found that the core of the PHF was restricted to a short truncated fragment of tau from the repeat domain. This was recently confirmed in a Nature paper in which cryoelectron microscopy was used to resolve the structure of the PHF at the atomic level (Fitzpatrick et al., 2017, Nature 547:185-190). However, until now it was not known how this fragment assembles into PHFs.

In a ground-breaking collaborative research project using electron microscopy, circular dichroism and X-ray fiber diffraction, researchers at the University of Sussex and TauRx Pharmaceuticals have succeeded in showing that the truncated fragment can be made to assemble into PHFs in the test tube (https://doi.org/10.1016/j.jmb.2017.09.007). This has potentially important consequences for understanding how the assembly process occurs at the molecular level, and how drugs that target tau aggregation work.