In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes

It is generally believed that amyloid p peptides (A beta) are the key mediators of Alzheimer's disease. Therapeutic interventions have been directed toward impairing the synthesis or accelerating the clearance of A beta. An equilibrium between blood and brain A beta exists mediated by carriers that transport A beta across the blood-brain barrier. Passive immunotherapy has been shown to be effective in mouse models of AD, where the plasma borne antibody binds plasma A beta causing an efflux of A beta from the brain. As an alternative to passive immunotherapy we have considered the use of A beta-degrading peptidases to lower plasma A beta levels. Here we compare the ability of three A beta-degrading peptidases to degrade A beta. Biotinylated peptidases were coupled to the surface of biotinylated erythrocytes via streptavidin. These erythrocyte-bound peptidases degrade A beta peptide in plasma. Thus, peptidases bound to or expressed on the surface of erythroid cells represent an alternative to passive immunotherapy. (c) 2007 Elsevier Inc. All rights reserved.