Biophysical properties of a tau seed

Zhiqiang Hou, Dailu Chen, Bryan D. Ryder, Lukasz Joachimiak

Research output: Contribution to journalArticlepeer-review

Abstract

Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed to drive pathological tau assembly in vitro, in cells and in vivo. We have previously described the isolation of monomeric pathogenic tau seeds derived from recombinant samples and tauopathy tissues but in-depth biophysical characterization of these species has not been done. Here we describe a chromatographic method to isolate recombinant soluble tau seeds derived from heparin treatment. We used biochemical and biophysical approaches to show that the seeds are predominantly monomeric and have the capacity to nucleate aggregation of inert forms of tau in vitro and in cells. Finally, we used crosslinking mass spectrometry to identify the topological changes in tau as it converts from an inert state to a pathogenic seed. Future studies will reveal the relationship between soluble seeds and structural polymorphs derived from tauopathies to help diagnose and develop therapeutics targeting specific tauopathies.

Original languageEnglish (US)
Pages (from-to)13602
Number of pages1
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Jun 30 2021

ASJC Scopus subject areas

  • General

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