The Effect of A beta(1-42) oligomers on APP Processing and A beta(1-40) Generation in Cultured U-373 Astrocytes

Background: Amyloid-beta (A beta) peptides are a family of proteins that are considered to be a principal aspect of Alzheimer's disease (AD), the most common cause of senile dementia affecting elderly individuals. These peptides result from the proteolytic processing of amyloid precursor protein (APP) by sequential cleavage mediated via beta- and gamma-secretases. Evidence suggests that an overproduction and/or a lack of degradation may increase brain A beta levels which, in turn, contribute to neuronal loss and development of AD. Objectives: In this study, we seek to determine what effect A beta has on APP processing in cultured astrocytes. Methods: Using the human astrocytoma cell line U-373, we investigated the effects induced by oligomeric A beta(1-42) treatment on the cellular levels/expression of APP and its products, C-terminal fragments alpha CTF and beta CTF, and A beta(1-40). In conjunction with these experiments, we examined the relative levels and activity of beta- and gamma-secretases in AP-treated astrocytes. Results: We report here that A beta(1-42) treatment of astrocytes increased the expression of APP and its cleaved products including A beta(1-40) in a time-dependent manner. Conclusions: These results suggest that activated astrocytes can contribute to the development of AD by enhancing levels and processing of APP leading to an increased production/secretion of A beta-related peptides. (C) 2015 S. Karger AG.