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 language | English |
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Pages (from-to) | 612-622 |
Number of pages | 11 |
Journal | Brain Pathology |
Volume | 19 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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