Amyloid-beta (Aβ) is a peptide produced in high amounts in Alzheimer’s disease (AD) causing impairment of synaptic long-term potentiation (LTP), a widely studied cellular model of learning and memory, and cognition. However, Aβ is present in normal brains at low concentration but its physiological function is still poorly known. Recently, we have demonstrated that low picomolar amounts of exogenously applied Aβ42 enhance LTP in vitro and memory in vivo and that endogenous Aβ is necessary for synaptic plasticity and memory on mice. Moreover, we showed that Aβ action involves alpha-7 nicotinic receptors, which are known to be involved in different brain functions including synaptic plasticity and memory. Indeed, our findings strongly support a model for Aβ effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well-known detrimental effect, culminating in dementia. The knowledge of both the physiological role and the hormetic effect of Aβ (a biphasic dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition), together with the clinical failure of anti-Aβ based therapy, raises several criticisms to the approaches aiming to decrease Aβ load, especially when suggested as prevention of the disease in healthy subjects.
|Titolo:||Physiological role of Amyloid-beta peptide and its implication in Alzheimer Disease|
|Data di pubblicazione:||2013|
|Appare nelle tipologie:||4.1 Contributo in Atti di convegno|