Researchers at Tel Aviv University have discovered encouraging findings that may help in the battle against Alzheimer's disease, the most common form of dementia that afflicts millions worldwide and that has no cure. The researchers' findings appear to indicate that mice with the disease could be cured by treating the genetic mutations that led them to develop Alzheimer's.
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“Research on Alzheimer's, like the development of medications to prevent and treat the disease, is at a critical point,” said Professor Danny Michaelson, head of the Rabin Center for Neurobiology and a faculty member of the Sagol School of Neuroscience at Tel Aviv University.
Over the past 30 years, research on Alzheimer’s Disease has concentrated on two fronts: The first is identifying a peptide (peptides are short chains of amino acids) known as amyloid beta, which clump together into plaque that contributes to the disease by blocking cell-to-cell signaling at synapses. The plaque may also activate immune system cells that trigger inflammation and devour disabled cells.
The second focal point for research has been familial Alzheimer’s, an inherited form of the disease that appears only in five percent of patients. According to Dr. Michaelson, “Eighty-five percent of research to develop treatments for Alzheimer’s Disease revolves around the beta amyloid peptide, but this method, which has dominated the field, has not led to any dramatic breakthrough in recent years.”
However, a new series of studies conducted in Israel and the United States that are to be published this week at the 21st annual Tel Aviv University Alzheimer’s Disease Conference show encouraging findings for therapies that take a different tack. These studies focus on Alzheimer’s Disease that occurs randomly, as in 95 percent of patients.
These patients are now known to have genetic risk factors that increase the likelihood of their contracting the disease. The most prominent of these factors is a genetic mutation known as APOE4, which occurs among 25 percent of the general population and 60 percent of people with Alzheimer’s Disease. People who carry one copy of this mutation (of two copies of the APOE gene, on which it appears) are four times more likely to develop the disease, while people who carry two copies of the mutation are eight times more likely to have it.
In a preliminary study conducted recently at Tel Aviv University, the human APOE gene was injected into mice in both its ordinary and pathological forms. In the study, headed by Dr. Ori Liraz, researchers found a similarity between the behavior of mice that carried the mutation and the behavior of human beings who suffer from Alzheimer’s Disease.
“Mice with the genetic mutation suffered behavioral changes such as memory and learning impairment, as patients with Alzheimer’s Disease do,” Dr. Michaelson said. Once the symptoms of the disease appeared, the researchers had to find out whether and how the damaged gene could be repaired. After a series of studies, they successfully repaired the mutation using two separate strategies.
In the first study, antibodies were developed that could identify the genetic mutation linked to Alzheimer’s Disease. When the antibodies were injected into month-old mice that carried both copies of the genetic mutation, they bonded to the mutation and neutralized its effect. At four months of age, the mice's behavior and some of the brain damage had improved. They were even able to perform learning tasks, indicating that the antibodies could help prevent the disease from developing among people who carry the mutation. The study, conducted at Tel Aviv University with the participation of doctoral student Ishai Luz, is being expanded to examine the effects of the antibodies on adult mice showing signs of the disease.
In another study conducted at Case Western Reserve University in Cleveland, Ohio, and continued at Tel Aviv University, researchers succeeded in repairing the genetic mutation and the cognitive and behavioral symptoms of Alzheimer’s Disease in lab mice.
Professor Gary Landreth launched the study and showed that a drug called bexarotene, which is used to treat cancer, affected the APOE gene. Later on, Tel Aviv researchers from Tel Aviv, led by doctoral student Anat Bam-Kagan, found that giving the drug to mice helped repair the damage of the APOE4 mutation. The researchers showed that adult mice with the mutation and symptoms of Alzheimer’s Disease improved after receiving an injection: They showed signs of decreased brain damage, behavioral improvement and increased ability to perform learning tasks.
The researchers presented this new approach at a scientific conference held in Italy in March.
This week, they will present the results at a conference directed by Dr. Michaelson and Professor Amos Korczyn, former head of the neurology department at Ichilov Hospital and a researcher of Alzheimer’s Disease.
“We are not ruling out the existing approaches in research,” Michaelson said. “But we believe other approaches should be included, too.”