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.

Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

“…Moreover, fast oscillatory activity is more disrupted both in AD patients [56, 57] and in AD animal models [54, 58, 59]. Thus, understanding the cellular basis of the changes in neural network activity and the alteration in neural network coupling induced by A β would help to explain the cellular basis of AD pathophysiology and also would reveal therapeutic strategies to reactivate such networks or reestablish their connections in order to palliate AD symptoms [60–62]. …”

Novel Insights into the Physiological Function of the APP (Gene) Family and Its Proteolytic Fragments in Synaptic Plasticity

“…During LTD, Aß was shown to have a facilitating role through mGluR and NMDA-R due to the altered glutamate recycling at synapses (Li et al, 2009; Chen et al, 2013). The pathological effects of Aß, especially Aß42, are discussed in detail elsewhere (Mucke and Selkoe, 2012; Wang H. et al, 2012; Ripoli et al, 2014; Salgado-Puga and Pena-Ortega, 2015) We only want to mention that under pathological conditions Aß has the opposite effects on synaptic plasticity: it facilitates LTD, depresses LTP, causes dendritic spine loss and leads to hippocampal hyperactivity (Selkoe, 2002; Busche et al, 2008; Shankar et al, 2008; Mucke and Selkoe, 2012; Fol et al, 2016). …”

Wine consumption, cognitive function and dementias – A relationship?

“…In a rat model, a moderate concentration of ethanol (0.8 g/kg) stimulated the release of acetylcholine while a higher concentration (2.4 g/kg) inhibited its release [115]. The formation of amyloid fibrillar plaques is also common in diseases such as Parkinson's disease, prion diseases, Down's syndrome and type II diabetes [116][117][118][119][120][121].…”