Researchers at New York University School of Medicine have come up with a novel way to prevent the accumulation of protein plaques that are the hallmark of Alzheimer's disease.
For unidentified reasons, a protein called amyloid beta aggregates into plaques, become toxic, eventually killing the neurons. These plaques are a sure- sign of Alzheimer's disease.
Now, two new animal studies have revealed for the first time that the deadly transformation of amyloid beta into plaques can be prevented through an interaction between amyloid beta and another protein called cystatin C.
Efrat Levy, Ph.D., Associate Professor in the Departments of Psychiatry and Pharmacology at NYU School of Medicine, and the lead author of the study said, although much work needs to be done, these new findings may open the door to new treatments for Alzheimer's disease that mimic the effects of cystatin C.
"We are really excited by these findings because recent studies show that cystatin C is protective against a variety of insults that cause cell death in the brain. Our potential therapeutic approach focuses on keeping amyloid beta in a water soluble form, preventing its accumulation in the brain, and thus slowing, halting, or reversing disease progression," Nature quoted Dr. Levy, as saying.
Receiving backing from the Alzheimer's Association, Dr. Levy's lab has already begun studies to develop a drug that will mimic the ability of cystatin C to bind to a non-pathological form of amyloid beta and thereby prevent its accumulation into plaques in the brain.
Many laboratories worldwide are pursuing ways to prevent the clumping of amyloid beta as possible therapies for the disease. It isn't known whether the protein actually causes Alzheimer's, but amyloid beta is one of the proteins implicated in the disease process.
The two studies used mice that were genetically engineered to produce human cystatin C as well as abundant amounts of amyloid beta plaques in their brains. The cystatin C bound to the soluble, non-pathological form of amyloid beta in these mice and inhibited the aggregation and deposition of amyloid beta plaques in the brain.
Dr. Levy said the study has revealed that cystatin C binds soluble amyloid beta also in the human brain, and has suggested that this binding inhibits its aggregation into insoluble plaques in humans.
She said that cystatin C production and body fluid levels vary among healthy individuals and can be influenced by certain hormones, aging, and certain pathological conditions.
Further, it was recently demonstrated that a genetic variation in the cystatin C gene in human populations is linked to a greater risk of developing Alzheimer's disease during aging.
Dr. Levy said, these findings suggest that even subtle modifications of cystatin C protein levels could affect amyloid beta accumulation and deposition in the brain, thereby modifying disease progression.
*Cystatin C is found in all body fluids and tissues of mammals. It is a jack-of-all-trades, playing a broad role in many functions, including cell proliferation and growth, modulation of the inflammatory response, and bone resorption. The protein also has been implicated in neuronal degeneration and repair of the nervous system.
"The work of Dr. Levy and colleagues offers important insights into how cystatin C may lower the risk for Alzheimer's disease, setting the stage for a new approach to therapy," said Ralph A. Nixon, M.D., Ph.D., Professor of Psychiatry and Cell Biology at NYU School of Medicine and Director of the Center for Dementia Research at the Nathan S. Kline Institute.
Both studies appear in the on-line November 18, 2007, edition of the journal Nature Genetics and will be published in its December 2007 issue