Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag

Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTPD-17). Pure tau in high yield is a requirement for in vitro evaluation of the protein's physiological and toxic functions. However, the preparation of recombinant tau is complicated by the protein's propensity to aggregate and form truncation products, necessitating the use of multiple, time-consuming purification methods. In this study, we investigated parameters that influence the expression of wild type and FTPD-17 pathogenic tau, in an attempt to identify ways to maximise expression yield. Here, we report on the influence of the choice of host strain, induction temperature, duration of induction, and media supplementation with glucose on tau expression in Escherichia coli. We also describe a straightforward process to purify the expressed tau proteins using immobilised metal affinity chromatography, with favourable yields over previous reports. An advantage of the described method is that it enables high yield production of functional oligomeric and monomeric tau, both of which can be used to study the biochemical, physiological and toxic properties of the protein. •Factors influencing the expression of wild type and FTPD-17 pathogenic tau were investigated in an attempt to maximise yield.•Soluble monomeric tau expression level was highest at 37 °C compared to 20 °C and 25 °C.•Media supplementation with 0.2% glucose did not significantly influence monomeric tau expression levels.•Circular dichroism confirmed that the purified tau proteins were mostly unfolded, with negative peaks around 200 nm.•The circular dichroism peaks shifted towards 220 nm following the preparation of Alzheimer-like filaments, suggesting secondary structure re-orientation towards β-sheets.•The tau proteins adopted classical fibrillisation similar to filaments isolated from the brains of Alzheimer's disease patients.