αv integrins mediate beta-amyloid induced inhibition of long-term potentiation

Abstract

Beta-amyloid (Aβ) is the principal component of the extracellular plaques present in patients with Alzheimer's disease. Several studies have recently shown that acutely applied Aβ inhibits the induction of LTP in the hippocampus. In the present studies, we have investigated the role of integrins in such Aβ-mediated block of LTP in the dentate gyrus in vitro and in the CA1 in vivo. Selective antibodies to the αv integrin subunit were found to prevent the Aβ 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 Aβ. In addition, a small molecule nonpeptide antagonist of αv-containing integrins and two other antagonistic ligands of integrins, superfibronectin and the disintegrin echistatin, also prevented the Aβ inhibition of LTP. These studies indicate that αv integrins may be important mediators of synaptic dysfunction prior to neurodegeneration in Alzheimer's disease.