David R. Schubert, Ph.D.
The Salk Institute for Biological Studies
La Jolla, California

2006 Investigator-Initiated Research Grant

Beta-amyloid, a tiny protein fragment and key suspect in Alzheimer's disease, is clipped from a molecule called amyloid precursor protein (APP). In order to study the relationship of APP, beta-amyloid and Alzheimer's disease, scientists depend heavily on mice that develop an Alzheimer-like disorder. Most of these mice are genetically altered to carry one or more of the mutated human genes that cause the rare inherited form of Alzheimer's disease.

David R. Schubert, Ph.D., and colleagues have identified a protein, dubbed modifier of cellular adhesion (MOCA), that appears to help regulate the processing of APP in cell cultures. Subsequently, they developed a genetically modified mouse with the naturally occurring mouse MOCA gene "turned off." These mice have elevated levels of APP and beta-amyloid, and they develop Alzheimer-like amyloid deposits as they age.

In this study, Dr. Schubert's team will cross the MOCA-less mice with mice carrying mutated human Alzheimer-causing genes. They hope to use the new mouse model to characterize the interactions of MOCA, APP and enzymes that help produce beta-amyloid. Findings from this work may demonstrate a potential role of MOCA in normal cell functions and Alzheimer's disease.