Alzheimer's disease (AD) is pathologically characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid beta-peptide (A beta) is the main component of senile plaques, and the pathological load of A beta in the brain has been shown to be a marker of the severity of AD. A beta is produced from the amyloid precursor protein by membrane proteases and is known to aggregate. Recently, immune-mediated cerebral clearance of A beta has been studied extensively as potential therapeutic strategy. In previous studies that used a purified A beta challenge in a mouse model of AD, symptomatic improvement was reported. However, a clinical Alzheimer's vaccine trial in the United States was stopped because of severe side effects. Immunization with the strong adjuvant used in these trials might have activated an inflammatory Th1 response. In this study, to establish a novel, safer, lower-cost therapy for AD, we tested an oral vaccination in a wild-type and a transgenic mouse model of AD administered via green pepper leaves expressing GFP-A beta. Anti-A beta antibodies were effectively induced after oral immunization. We examined the immunological effects in detail and identified no inflammatory reactions. Furthermore, we demonstrated a reduction of A beta in the immunized AD-model mice. These results suggest this edible vehicle for A beta vaccination has a potential clinical application in the treatment of AD. (C) 2010 Elsevier Inc. All rights reserved.