The X11 adaptor proteins and Alzheimer's disease. (360G-Wellcome-078662_Z_05_Z)

Work from our and a number of other laboratories has demonstrated that X11a an d X11b inhibit APP processing and Ab production. However, the molecular mechan isms that underlie this effect are not known. This project is to gain insight into these mechanisms. Release of Ab from APP involves proteases termed secret ases and one key goal of this project is to determine whether theX11s influenc e secretase function. A second key goal is to determine whether X11 inhibition of Ab production involves altered trafficking of APP and/or APPsecretases. Fi nally, we have found that the X11s are involved in neuronal copper metabolism and that one of the secretases (BACE1) is a copper binding protein. Disruption to copper homeostasis is believed to contribute to Alzheimer's disease. The f inal goal is to understand further how copper is delivered to BACE1 and whethe r it influences BACE1 function and Ab production.