Transglutaminases and transglutaminase-catalyzed cross-links colocalize with the pathological lesions in Alzheimer's disease brain

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Abstract

Alzheimer's disease (AD) is characterized by pathological lesions, in particular senile plaques (SPs), cerebral amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly consisting of self-aggregated proteins amyloid beta (Abeta) and tau, respectively. Transglutaminases (TGs) are inducible enzymes, capable of modifying conformational and/or structural properties of proteins by inducing molecular covalent cross-links. Both Abeta and tau are substrates for TG cross-linking activity, which links TGs to the aggregation process of both proteins in AD brain. The aim of this study was to investigate the association of transglutaminase 1 (TG1), transglutaminase 2 (TG2) and TG-catalyzed cross-links with the pathological lesions of AD using immunohistochemistry. We observed immunoreactivity for TG1, TG2 and TG-catalyzed cross-links in NFTs. In addition, both TG2 and TG-catalyzed cross-links colocalized with Abeta in SPs. Furthermore, both TG2 and TG-catalyzed cross-links were associated with CAA. We conclude that these TGs demonstrate cross-linking activity in AD lesions, which suggests that both TG1 and TG2 are likely involved in the protein aggregation processes underlying the formation of SPs, CAA and/or NFTs in AD brain.

Original languageEnglish
Pages (from-to)612-622
Number of pages11
JournalBrain Pathology
Volume19
Issue number4
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Cerebral Amyloid Angiopathy
  • Cross-Linking Reagents
  • Female
  • Humans
  • Immunohistochemistry
  • Journal Article
  • Male
  • Middle Aged
  • Neocortex
  • Neurofibrillary Tangles
  • Neurons
  • Phosphorylation
  • Plaque, Amyloid
  • Research Support, Non-U.S. Gov't
  • Transglutaminases
  • tau Proteins

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