A team of San Francisco scientists studying Alzheimer's disease has found the interaction of two brain proteins may be a critical factor in development of the debilitating disorder.
Both proteins have been the focus of intense scientific scrutiny because of their independent roles in different diseases and basic cell biology. The current study reveals a novel interaction between the two that could help explain the death of nerve cells associated with Alzheimer's disease, or AD. Understanding this process could lead to development of better treatments to prevent or slow the degeneration of nerve cells that causes memory loss or disturbed thinking that are symptoms of the illness.
The research, conducted by researchers from the Gladstone Institute of Neurological Disease (GIND) and the University of California San Francisco, is reported in the new issue (June 22) of the Proceedings of the National Academy of Sciences.
One of the proteins, amyloid precursor protein, or APP, is normally found at high levels in the brain, but its function is largely unknown. The second protein is p53, which under certain conditions turns on an internal cell suicide process that leads to the death of the cell. In the case of nerve cells, this process can be devastating to the brain because most of these cells are irreplaceable.
Mutant forms of APP are associated with certain forms of AD, but how they cause the death of brain cells has been a mystery. Now the new research findings provide some clues.
The researchers, led by Gladstone staff research scientist Xiao Xu, MD, PhD, and Lennart Mucke, MD, director of the GIND and associate professor of neurology and neuroscience at UCSF, found that normal APP--known as "wild-type" APP--provides a protective function against nerve cell death, inhibiting the p53-induced suicide process in cell cultures. Findings showed mutant forms of APP do not provide this protection.