Christopher C. J. Miller, Ph.D.
Institute of Psychiatry
London, England

2006 Investigator-Initiated Research Grant

One of the characteristic features of Alzheimer pathology is the presence of amyloid plaques, abnormal structures made up in part by protein fragments known as beta-amyloid. Beta-amyloid is formed when its parent protein, the amyloid precursor protein (APP), is cut by enzymes known as beta-secretase (BACE1) and gamma-secretase.

Christopher Miller, PhD and colleagues, as well as other investigators, have found that another protein called X11alpha binds to APP and prevents it from being cut, thereby preventing the formation of beta-amyloid. They have found, however, that X11alpha is also involved in the metabolism and processing of copper, which is an important component of numerous enzymes.

Alterations in copper metabolism have been implicated in Alzheimer's disease for several years, but the mechanisms involved are unknown. Dr. Miller and colleagues have also shown that BACE1 also binds copper, so another possible role for X11alpha is that it alters the delivery of copper to BACE1.

The researchers plan to extend their studies of X11alpha, BACE1 and copper metabolism to understand how these enzymes interact with copper and with APP to influence the production of beta-amyloid. Their goal is to reveal targets that may be useful for the development of new therapeutic agents for Alzheimer's disease.