Jorge Busciglio, Ph.D.
University of California
Irvine, California

2003 Investigator-Initiated Research Grant

As Alzheimer’s disease progresses, brain cells (neurons) develop dystrophy—gradually shrinking and losing their connections with other neurons. Researchers have been able to recreate and study this process in the laboratory by exposing isolated neurons to the protein fragment beta-amyloid—the prime suspect in Alzheimer’s. One of the hallmarks of Alzheimer’s disease is abnormal beta-amyloid deposits called plaques lying between neurons, and Jorge Busciglio and his colleagues have discovered that one of the earliest responses inside cells is the abnormal gathering of focal adhesion (FA) proteins near the plaques.

Busciglio’s team first demonstrated this FA protein clumping in cells grown in the laboratory, and in the current study they are trying to confirm that this takes place inside the neurons of people with Alzheimer’s disease. To that end, they will use advanced microscope technology to examine brain tissue from people who died with the disease. The researchers will also investigate their hypothesis that beta-amyloid induces FA protein clumps by derailing the transport systems that move proteins around inside cells. If this idea is borne out, neuronal dystrophy in Alzheimer’s disease might be prevented by therapies that protect transport of FA proteins within the cell.