Amyloid beta peptides and glutamatergic synaptic dysregulation

Abstract

Alzheimer's disease (AD) is a major neurodegenerative disorder in which overproduction and accumulation of amyloid beta (Abeta) peptides result in synaptic dysfunction. Recent reports strongly suggest that in the initial stages of AD glutamate receptors are dysregulated by Abeta accumulation resulting in disruption of glutamatergic synaptic transmission which parallels early cognitive deficits. In the presence of Abeta, 2-amino-3-(3-hydoxy-5-methylisoxazol-4-yl) propionic acid (AMPA) glutamate receptor function is disrupted and the surface expression is reduced. Abeta has also been shown to modulate N-methyl-d-aspartate receptors (NMDARs) and metabotropic glutamate receptors. The Abeta mediated glutamate receptor modifications can lead to synaptic dysfunction resulting in excitotoxic neurodegeneration during the progression of AD. This review discusses the recent findings that glutamatergic signaling could be compromised by Abeta induced modulation of synaptic glutamate receptors in specific brain regions.