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

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. (C) 2012 Elsevier Inc. All rights reserved.