Alzheimer's Disease (AD) is a debilitating neurodegenerative disease affecting a significant and growing portion of the elderly population. Aß immunization has shown great promise for treatment of AD and further trials are currently underway, however the approach has potentially harmful side effects including hemorrhaging and inflammation in the brain. Our long term objective is to develop a series of novel recombinant antibodies that can be used as part of an effective passive immunization approach for treating or preventing AD while controlling potential inflammation in the CNS. Engineered antibody therapeutics are already in use for cancer and infectious disease, and offer an exciting new platform for neurological disease drug discovery and therapeutics This project specifically targets toxic protein misfolding in Alzheimer's disease by targeting beta-amyloid production and processing with engineered antibody fragments that can cleave the beta-amyloid petide into non-toxic products. The project will also have direct applications to related diseases such as Parkinson's, Huntington's and ALS.