Hormetic effect of amyloid-beta peptide in synaptic plasticity and memory

Abstract

One of the hot topics in Alzheimer’s disease research field is the “amyloid hypothesis” postulating that the increase and deposition of beta-amyloid peptides (A-beta) is the main pathogenetic factor. However, antiamyloid-based therapies have so far been a failure and, most importantly, growing evidences suggest that A-beta has important physiologic functions. Based on our previous findings demonstrating that low concentrations of A-beta enhanced both synaptic plasticity and memory, whereas high concentrations induced the well-known impairment of cognition, here we show that A-beta acts on hippocampal long-term potentiation and reference memory drawing biphasic dose-response curves. This phenomenon, characterized by low-dose stimulation and high-dose inhibition and represented by a U-shaped or inverted-U-shaped curve, resembles the characteristics of hormesis. The A-beta double role raises important issues on the use of A-beta level reducing agents in Alzheimer’s disease.