Impact of Sterilization Methods on the Seeding Ability of Human Tau Proteopathic Seeds

J Neuropathol Exp Neurol. 2021 Oct 26;80(10):912-921. doi: 10.1093/jnen/nlab087.

Abstract

The protein tau, when misfolded in neurodegenerative diseases, has several prion-like properties including being able to spread by cell-to-cell transfer, induce templated seeding, and exist in distinct conformational strains. These properties of transmission may present health hazards when lesion-containing biospecimens are used in research and neuropathology laboratories. We evaluated the impact standard sterilization and cleaning methods have on the capacity of tau seeds to induce aggregation. We employed a previously developed, highly sensitive FRET-based biosensor assay to assess remnant tau seeding after exposure to these procedures. For tau species derived from human Alzheimer disease tissue (brain homogenate and sarkosyl-insoluble fibrils), both autoclaving and incubation in 90.6% formic acid were sufficient to reduce tau bioactivity. By contrast, boiling was not always effective in completely blocking bioactivity in the seeding assay. Notably, only formic acid incubation was able to produce a similar reduction in tissue from a P301L mutant tau mouse model of tauopathy. Our study highlights nuances in methods for inactivation of tau seeding which may support adapted tissue processing procedures, especially in research settings. These findings also highlight the importance of universal precautions when handling human neuropathological and research laboratory materials.

Keywords: Alzheimer disease; Safety standards; Sterilization; Tau; Tauopathies; Transmissibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Animals
  • Brain / drug effects
  • Brain / pathology*
  • Chromatography, Gel / methods
  • Formates / pharmacology
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Transgenic
  • Sterilization / methods*
  • Tauopathies / pathology
  • tau Proteins / antagonists & inhibitors
  • tau Proteins / isolation & purification*

Substances

  • Formates
  • MAPT protein, human
  • tau Proteins
  • formic acid