In Vitro Amplification of Pathogenic Tau Seeds from Neurodegenerative Disease Patient Brains

Abstract

Aggregated microtubule-associated protein tau (tau) is the hallmark lesion of a group of neurodegenerative diseases, termed tauopathies. Normal endogenous tau is highly soluble and intrinsically disordered when it is not bound to microtubules. Pathological tau proteins are aggregates of bioactive filaments capable of inducing their normal counterparts into pathological conformations that are human tauopathy dependent. Taking advantage of this feature, we established an in vitro seeding reaction to amplify faithfully human-derived tau strains. This approach allows us to expand the quantity and improve the quality of pathogenic tau strains derived from human patient postmortem brains and to further understand tau pathogenesis in models of tauopathy. Here, we describe the approach to generate human pathogenic tau using human-derived tau seeds and recombinant human tau in vitro.