Cellular and network mechanisms underlying memory impairment induced by amyloid β protein.

Abstract

It has long been known that amyloid ß protein (Aß) plays a key role in Alzheimer's Disease (AD) and in Down Syndrome cognitive decline. Recent findings have shown that soluble forms of Aß (mostly Aß oligomers; Aßo), rather than insoluble forms (fibrils and plaques), are associated with memory impairments in early stages of AD. Since synaptic plasticity and oscillatory network activity are required for memory formation, consolidation and retrieval, numerous attempts have been made to establish whether or not Aßo-induced alterations in synaptic plasticity and oscillatory network activity cause memory impairment. Despite a wealth of uncorrelated experimental evidence, such a relationship remains elusive. Furthermore, the specific cellular mechanisms underlying these disruptions remain to be determined. This review will discuss recent findings about the cellular and network mechanisms involved in Aßo-induced alterations of network oscillations and synaptic plasticity that could be responsible for the learning and memory impairments observed in early AD. Additionally, we will review some of the signal transduction pathways involved in these deleterious effects, which are revealing promising therapeutic targets to ease Aßo-induced brain dysfunction and treat AD.