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 language | English (US) |
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Pages (from-to) | 983-989 |
Number of pages | 7 |
Journal | Journal of neuropathology and experimental neurology |
Volume | 59 |
Issue number | 11 |
DOIs | |
State | Published - 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