Amplification of Tau fibrils from minute quantities of seeds

Biochemistry. 2014 Sep 16;53(36):5804-9. doi: 10.1021/bi501050g. Epub 2014 Aug 29.

Abstract

The propagation of Tau pathology in Alzheimer's disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Brain / metabolism
  • Heparin / chemistry
  • Humans
  • Microscopy, Electron
  • tau Proteins / chemistry
  • tau Proteins / metabolism*
  • tau Proteins / ultrastructure

Substances

  • tau Proteins
  • Heparin