β-amyloid oligomers affect the structure and function of the postsynaptic region: Role of the Wnt signaling pathway

Abstract

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. Synaptic dysfunction is an early manifestation of AD. The cellular mechanism by which β-amyloid peptide (Aβ) affects synapses remains unclear. Aβ oligomers target synapses in cultured rat hippocampal neurons suggesting that they play a key role in the regulation of synapses. Objective: The aim of this work is to study the effect of Aβ oligomers on the central synapses and the possible role of the Wnt signaling pathway in preventing the Aβ effects. Methods: We used rat hippocampal neurons, immunofluorescence and western blot procedures to detect synaptic proteins. Results: Aβ oligomers induced a reduction of the postsynaptic density protein 95 (PSD-95) and the NMDA glutamate receptors. We found that Wnt-5a, a noncanonical Wnt ligand, prevents the decrease triggered by Aβ oligomers in the glutamate receptor and PSD-95. Conclusion: Altogether, our results suggest that Aβ oligomers decrease the synaptic responses by affecting the postsynaptic region at different levels. The Wnt signaling activation prevents synaptic damage induced by Aβ, which raises the possibility of a new therapeutic intervention for the treatment of synaptic changes observed in AD. Copyright © 2008 S. Karger AG.