Profile of beta-amyloid in response to beta-amyloid vacc

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The accumulation of amyloid in transgenic mice has been reduced by vaccination with either Abeta peptide or passive immunization with anti-Abeta. However, the mechanism by which vaccination works is poorly understood, especially as in at least one case, Abeta peptide administration did not clear CNS amyloid efficiently, even though it did correct cognitive impairment associated with amyloid accumulation in these mice. As it is not clear what type of Abeta is the target for vaccination. The first aim of this study is to examine which Abeta species are eliminated by vaccination. I will then attempt to identify which epitope of antibodies elicited by vaccination respond to fibrillar as opposed to diffuse amyloid. The conceptional mechanism of Abeta vaccination is that elicited anti-Abeta antibodies enhance microglial phagocytosis of Abeta leading to the clearance of Abeta from the brain. However, our, and other's data suggest that some interplay between peripheral and CNS Abeta also influences clearance of Abeta from the brain. Therefore, I will examine the effects of Abeta vaccination on Abeta levels in plasma. These two studies will aid in understanding the molecular basis of Abeta vaccination therapy, and suggest new strategies to design an antibody for passive immunization therapy. Based on evidence to be obtained from this study, I will isolate monoclonal antibodies from the mouse showed high Abeta clearance efficiency, and will test the effects of antibody in memory impairment using AD model mice.