Transglutaminase-induced cross-linking of tau proteins in progressive supranuclear palsy

Magdalena O. Zemaitaitis, John M. Lee, Juan C. Troncoso, Nancy A. Muma

Research output: Contribution to journalArticle

Abstract

The mechanisms leading to the abnormal self-polymerization of tau into straight and paired helical filaments (PHFs) and neurofibrillary tangles (NFT) in Alzheimer disease (AD) and progressive supranuclear palsy (PSP) are not known. However, transglutaminase-induced cross-linking of PHF-tau was observed in AD and thus may also contribute to the formation of NFT in other neurodegenerative disorders including PSP. Tissue homogenates from PSP and normal age-matched controls were used to immunoaffinity-purify proteins containing transglutaminase-induced ε-(γ-glutamyl) lysine cross-links. The immunoaffinity-purified proteins were then examined on immunoblots with a PHF-tau antibody, PHF-1. There were significantly higher levels of ε-(γ-glutamyl) lysine cross-linking of PHF-tau in globus pallidus and pons regions of PSP cases compared to barely detectable cross-links in controls. The occipital cortex, an area spared from neurofibrillary pathology in PSP, showed no detectable cross-linking of PHF-tau protein in either PSP cases or control cases. Double-label immunofluorescence demonstrated the colocalization of the cross-link and PHF-tau in NFT in pons of PSP. Previous studies and present data are consistent with the hypothesis that transglutaminase-induced cross-linking may be a factor contributing to the abnormal polymerization and stabilization of tau in straight and PHFs leading to neurofibrillary tangle formation in neurodegenerative diseases, including PSP and AD.

Original languageEnglish (US)
Pages (from-to)983-989
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume59
Issue number11
DOIs
StatePublished - Jan 1 2000

Keywords

  • Alzheimer disease
  • Cross-linking
  • Neurodegeneration
  • Progressive supranuclear palsy (PSP)
  • Tau
  • Tauopathy
  • Transglutaminase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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