αv intearins mediate beta-amyloid induoced inhibition of long-term potentiation

Beta-amyloid (A beta) is the principal component of the extracellular plaques present in patients with Alzheimer's disease. Several Studies have recently shown that acutely applied A beta inhibits the induction of LTP in the hippocampus. In the present Studies, we have investigated the role of integrins in Such A beta-mediated block of LTP in the dentate gyrus ill Vitro and in the CA1 in vivo. Selective antibodies to the alpha v interin subunit were found to prevent the A beta inhibition of LTP, both in the dentate gyrus in vitro and in the CA1 in vivo. In contrast, two control antibodies did not prevent such action of A beta. In addition, a small molecule, nonpeptide antagonist of alpha v-containing integrins and two other antagonistic ligands of integrins, superfibronectin and the disintegrin echistatin, also prevented the A beta inhibition of LTP. These Studies indicate that alpha v integrins may be important mediators of synaptic dysfunction prior to neurodegeneration in Alzheimer's disease. (C) 2007 Elsevier Inc. All rights reserved.