An Additive-Free Model for Tau Self-Assembly

Abstract

Tau is a natively unfolded protein that contributes to the stability of microtubules. Under pathological conditions such as Alzheimer’s disease (AD), tau protein misfolds and self-assembles to form paired helical filaments (PHFs) and straight filaments (SFs). Full-length tau protein assembles poorly and its self-assembly is enhanced with polyanions such as heparin and RNA in vitro, but a role for heparin or other polyanions in vivo remains unclear. Recently, a truncated form of tau (297–391) has been shown to self-assemble in the absence of additives which provides an alternative in vitro PHF model system. Here we describe methods to prepare in vitro PHFs and SFs from tau (297–391) named dGAE. We also discuss the range of biophysical/biochemical techniques used to monitor tau filament assembly and structure.