Upregulation of tPA/plasminogen proteolytic system in the periphery of amyloid deposits in the Tg2576 mouse model of Alzheimer's disease

Joo Yong Lee, Hee Seok Kweon, Eunsil Cho, Jee Young Lee, Hyae Ran Byun, Dong Hou Kim, Yang Hee Kim, Pyung Lim Han, Jae Young Koh

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Although the tissue plasminogen activator (tPA)/plasminogen/plasmin proteolytic system is thought to modulate the catabolism of amyloid-β (Aβ), in vivo evidence remains insufficient. In the brain of human amyloid precursor protein transgenic Tg2576 mice, we found co-accumulation of tPA and plasminogen at the periphery of compact amyloid deposits, mainly Aβ42-cored plaques, as well as in the walls of blood vessels with cerebral amyloid angiopathy (CAA). This tPA/plasminogen system contained high levels of proteolytic activity. High levels of tPA were also found in reactive astrocytes with increased Aβ42 expression, whereas plasminogen was found only in neurons. When the brain sections of Tg2576 mice were treated with both tPA and plasminogen, levels of thioflavin-S fluorescence, congophilicity and birefringence in the compact amyloid plaques were significantly reduced, and the ultrastructure of Aβ42-fibrils was disrupted. These results suggest that the assembled Aβ42 may promote upregulation of the tPA/plasminogen proteolytic system, which can modulate the deposition of amyloid plaques in vivo.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalNeuroscience Letters
Volume423
Issue number1
DOIs
StatePublished - 9 Aug 2007

Keywords

  • Amyloid-β
  • Cerebral amyloid angiopathy
  • In situ zymography
  • Plasmin
  • Protease

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