Tau Oligomers as Pathogenic Seeds: Preparation, Characterization, and Propagation In Vitro and In Vivo

Abstract

Tau oligomers have been shown to be the main toxic tau species in several neurodegenerative disorders. To study tau oligomers, we have developed reagents and established methods for the reliable preparation, isolation, and detection of tau oligomers as well as their seeding and propagation both in vitro and in vivo. Detailed below are methods for isolation of tau oligomers from brain tissues and detection of tau oligomers using tau oligomer-specific antibodies by biochemical, immunohistochemical, and biophysical methods. Further, methods for evaluating the biological activity of the tau oligomers including their effects on synaptic function, seeding, and propagation in cell models and in vivo are also described.

Keywords: Amyloid seeding; Brain-derived tau oligomers; Fluorescent amyloid multi-emission spectra microscopy; Long-term potentiation; Primary cortical neurons; Proteolysis; Sucrose density gradient; Tau oligomers; TauopathiesTautauopathies.