In vivo vascular damage, leukocyte activation and inflammatory response induced by beta-amyloid.

Abstract

beta-amyloid toxicity is central to the pathology of Alzheimer's disease. Recent evidence implicates vascular dysfunction as a contributing factor to the dementia of Alzheimer type. Using intravital microscopy we demonstrate that in vivo administration of beta-amyloid produces extensive vascular disruption including endothelial and smooth muscle damage, adhesion and migration of leukocytes across arteries and venules. Amyloid angiopathy with vascular damage and inflammatory changes are hallmarks in the brains of Alzheimer disease victims. The vascular actions of beta-amyloid are distinct from the neurotoxic properties of the peptide and were prevented by the free radical scavenging enzyme superoxide dismutase. Oxygen radical mediated vascular dysfunction may induce ischemic and inflammatory responses leading to neurodegeneration as seen in Alzheimer's disease.