Maladie d'Alzheimer, peptide β-amyloïde et synapses

Abstract

Alzheimer's disease (AD) is the first cause of dementia that leads to insidious and progressive loss of memory and cognitive functions. In the early stages of AD, there is a strong correlation between memory impairment and cortical levels of soluble amyloid-β peptide oligomers (Aβ). It has become clear that Aβ disrupt glutamatergic synaptic function, which in turn may lead to the characteristic cognitive deficits. Conversely, experiments in rodents have conforted the notion that Aβo impairs synaptic transmission and plasticity, and that mouse models with increased production of these oligomers display cognitive impairment. Many studies have attempted to determine the mechanisms by which Aβo disrupt synaptic plasticity and mediate their detrimental effect, but the actual pathways are still poorly understood. Here we review this thriving area of research which aims at undertanding the mechanisms of synaptic dysfunction in the early phase of AD, and its consequences on the activity of neural circuits.