MUCOSAL ABETA VACCINATION; MODULATING THE IMMUNE RESPONSE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abeta immunotherapy has potential for preventing and possibly treating Alzheimer¿s disease (AD) in humans. Studies in genetically-engineered AD mouse models have consistently demonstrated efficacy of the Abeta vaccine both in lowering CNS Abeta and improving cognition without any adverse effects. However, the first human clinical trial was halted due to meningoencephalitis in approximately 6% of patients; recognition of the full-length Abeta immunogen as a self-protein may have attributed to these adverse events. Non-human primates, including Caribbean vervets (Chlorocebus aethiops), have the same amyloid precursor protein (APP) and Abeta as humans, and have age-related cerebral plaque deposition. Thus, they may serve as a better animal model for studying Abeta clearance and immune responses to Abeta vaccination. We are training vervets for behavioral testing of cognitive functions and will begin Abeta vaccination in the next several months. Our goals are to characterize the humoral and cellular immune responses to a novel Abeta vaccine and to determine the vaccine¿s efficacy in lowering Abeta within the nervous system and improving cognition.