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Title: Ageing and amyloid-beta peptide deposition contribute to an impaired brain tissue plasminogen activator activity by different mechanisms
Authors: Cacquevel, Mathias
Launay, Séverine
Castel, Hervé
Benchenane, Karim
Chéenne, Simon
Buée, Luc
Moons, Lieve
Delacourte, André
Carmeliet, Peter
Vivien, Denis # ×
Issue Date: Aug-2007
Publisher: Blackwell Science
Series Title: Neurobiology of Disease vol:27 issue:2 pages:164-173
Abstract: Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder in the ageing population. It is characterized by the cerebral accumulation of toxic amyloid-beta peptide assemblies (Aβ). The serine protease plasmin, which is generated from the inactive zymogen plasminogen through its proteolytic cleavage by tissue- (tPA) or urokinase-type plasminogen activator, has been implicated in the catabolism of Aβ peptides. In this report, we studied the regulation of tPA activity in vivo during ageing in normal mice and in a mouse model of AD characterized by an exacerbated endogenous Aβ accumulation. We observed that cerebral tPA activity was decreased during ageing in normal mice and that this effect was worsened in mice overproducing Aβ peptides. These phenomena result, respectively, from a decrease in tPA expression and from an increase in the production of one of the tPA inhibitors, the plasminogen activator inhibitor type 1 (PAI-1). A similar study in sporadic AD and age-matched control brain tissues revealed that the tPA proteolytic activity was negatively correlated to Aβ peptides levels supporting the data observed in mice. Altogether, our data support a model in which amyloid deposition induces a decrease in tPA activity through the overproduction of PAI-1 by activated glial cells.
URI: 
ISSN: 0969-9961
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Molecular and Vascular Biology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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