Carvedilol as a potential novel agent for the treatment of Alzheimer's disease

Oligomeric beta-amyloid (A beta) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective beta-adrenergic receptor blocker, significantly attenuates brain oligomeric beta-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable learning thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD. (C) 2011 Elsevier Inc. All rights reserved.