Hormesis and Amyloid-β Protein: Physiology or Pathology?

Abstract

Hormesis is the concept that low doses of a toxin can have beneficial effects while high doses are harmful. This is also known as the inverted-U shaped dose-response curve. Hormesis appears to be a universal law for the function of memory mimetics. Amyloid-β protein is widely recognized to be a toxic agent responsible for plaque formation in Alzheimer's disease. In high doses it also produces amnesia. In lower, physiological doses, it enhances long term potentiation and memory. Blocking amyloid-β protein in animals without overproduction of the protein results in amnesia. At low doses, amyloid-β also increases neurite outgrowth, produces presynaptic enhancement, and may quench oxidative damage. It is postulated that both over- and underproduction of amyloid-β can lead to memory deficits. This is similar to a number of hormonal diseases, e.g., thyroid, where both low and high levels produce disease.