Amyloid plaques can primarily be targeted in two ways; by decreasing their formation or by enhancing their removal and clearance. A number of naturally occurring processes in the brain perform this clearance function. The enzyme neprilysin (NEP) is one such example of a mechanism that enhances the clearance of amyloid from the brain. The investigator will explore the use of neprilysin using two different methods to tether the enzyme onto circulating blood cells. These strategies should ultimately lead to the increased clearance of plasma A?, and in turn a reduction of brain A? through equilibrium between the CNS and plasma levels of the A? peptide. In the proposed studies, the PI will investigate these two alternative strategies for lowering A? levels using a transgenic mouse model of AD.