Scientists have provided new details about how proteins used to destroy bacteria and viruses may help treat Alzheimer's disease.
Gunnar K. Gouras, associate professor of neurology and neuroscience at Weill Medical College of Cornell University, New York, and colleagues provide new insights into how these proteins, called antibodies, reduce the main hallmarks of Alzheimer's disease and raise hopes for a vaccine against the disease.
"Antibodies are probably the most promising experimental approach to fight Alzheimer's disease at this time," Gouras says. "The discoveries made using antibodies are so encouraging that results of ongoing vaccine trials against the disease are much anticipated."
Alzheimer's disease, the most common form of dementia, gradually destroys a person's memory and ability to learn, communicate, and carry out daily activities. According to the American Health Assistance Foundation, more than 4.5 million people in the United States live with the disease and more than 26 million people are affected worldwide. By 2050, the number of people who will suffer from the disease is estimated to nearly triple in the United States and to be four times as high worldwide.
Although no cure for the disease is available yet, scientists are actively looking for new treatments. One of the main goals of such treatments is to destroy clumps of a protein called beta amyloid, which are found in the brains of people with the disease, either inside the nerve cells or around them. Antibodies have been shown to be effective at removing these clumps but how they do it is not completely understood.
In their new study, appearing as the cover story of the June 29 issue of the Journal of Biological Chemistry, Gouras and his colleagues provide new details about how the antibodies attack these clumps inside the nerve cells. The study was selected as a 'Paper of the Week' by the journal's editor, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.
Using cultured cells from mice, the scientists showed that the antibodies first bind to the surface of the cells and connect to a protein called amyloid precursor protein (APP), which is already present on the cell surface. Then both proteins are internalized inside the cell.
Once inside the cell, APP is broken down into pieces, some of which are the amyloid beta proteins. If the antibodies are not present, the proteins start clustering and ultimately kill the cell. The scientists showed that the antibodies prevent this from happening by reducing accumulation of the amyloid beta proteins in vesicles inside the cell called endosomes.
"A lot of research has been done on protein clusters outside nerve cells," Gouras says. "In this study, we investigated for the first time what happens inside the cells and how antibodies can help prevent clusters from forming."
The researchers also found that the antibodies helped restore communication between nerve cells. In Alzheimer's patients, the protein clusters alter parts of the cell surfaces , the synapses , that help nerve cells talk to one another. As a result, thoughts are not transmitted, memory is lost, and new learning is hindered. But Gouras and his team showed that the antibodies cleared the protein clusters and helped cells talk to one another again.