Huaxi Xu, Ph.D.
Rockefeller University
New York, New York

2003 Investigator-Initiated Research Grant

Much Alzheimer’s disease research is closely focused on a single molecular event, the processing of amyloid precursor protein (APP). One of the resulting protein fragments, beta-amyloid, forms abnormal aggregates in the brain and is the prime suspect in the death of brain cells in the disease. Scientists have discovered that an entire team of proteins, termed the gamma-secretase complex, works together to cut APP and release beta-amyloid. One of these proteins is presenilin, whose role in Alzheimer’s is suspected from the fact that mutations in the gene for presenilin lead to an inherited, early-onset form of the disease. However, it is not clear exactly what role presenilin plays in the secretase complex or whether it also contributes to Alzheimer’s in other ways.

Huaxi Xu, PhD, and colleagues have shown in previous research that presenilin could play a role in protein trafficking, the process of guiding proteins from cellular “construction sites,” through various structural modifications, to their final destinations within the cell. In this study, the researchers will try to determine exactly how presenilin affects protein trafficking, and also whether it plays a role in the trafficking of the other proteins in the gamma-secretase complex, as well as trafficking of APP itself.