Amyloid plaques are sticky clumps that can form in the brain and damage healthy cells. For many years, clinicians have tried to figure out how to remove the brain plaques that trigger Alzheimer's disease. Researchers at Washington University who are exploring the plaques discovered another AD protein and a type of antibody that have the potential to clear the plaques.
Antibody Type Clears Away Brain Plaques
Beta-amyloid is a protein that plays an important role in growth and repair of nerve cells. However, as a person grows older, a corrupted form of the protein can damage nerve cells which leads to Alzheimer's disease. The protein affects nerve cells by clumping together to form a sticky substance called plaque.
The corrupted form of beta-amyloid destroys neurons in two ways:
1. The protein clumps can block the synapses of nerve cells that prevent their signaling function.
2. The protein clumps can induce an immune response that causes inflammation. The immune cells may also devour cells disabled by the clumps.
Since clinicians have not figured out yet how to clear these clumps from the brain, no medication has been developed to cure the neurological disorder. But the researchers at Washington University bumped into two important finds that may lead to an effective treatment, after investigating the plaques.
The first thing they found was another type of protein associated with Alzheimer's disease called APOE. This is a gene that instructs the creation of the protein apolipoprotein E, while the protein combines lipids to form lipoproteins. Lipoproteins are responsible for packing cholesterol and other forms of fat through the bloodstream.
In the study, the researchers detected small amounts of APOE in the brain burrowed within amyloid plaques. Certain variants of the gene have been found to greatly increase the risk of Alzheimer's disease. And reducing the overexpression of the gene may decrease the injury caused by the plaques.
When the researchers further investigated to find out whether or not the gene can be removed, they looked into antibodies that can bind with APOE. They used mice models with a genetic disposition to develop amyloid plaques and replaced their APOE gene with the human variant.
After that, they tested several antibodies that can recognize the human APOE gene for six weeks, along with another mice model under placebo for a similar amount of time. The result led to the discovery of the second important find in the study. The HAE-4 antibody has been found to be capable of reducing the number of brain plaques by 50 percent.
"Many people build up amyloid over many years, and the brain just can't get rid of it. By removing plaques, if we start early enough, we may be able to stop the changes to the brain that result in forgetfulness, confusion and cognitive decline," expressed Dr. David Holtzman, the senior author of the study and head of the department of neurology at WU School of Medicine in St. Louis.
They observed two traits in the antibody that bind with APOE. First, it can attract immune cells patrolling the brain area that can destroy both the antibody and its targets. Second, it does not bind to the APOE in the bloodstream.
"It turns out that the APOE in the plaques has a different structure than the form of APOE found in the blood. The HAE-4 antibody recognized only the form found attached to the plaques in the brain," Dr. Holtzman explained.
The use of an antibody to remove the plaque can raise concern about the inflammatory response of the immune system in the brain. But Dr. Holtzman said that the special antibody binds only a very small part of the plaque which does not cause a major immune response that often leads to adverse side effects.
The researchers are planning to conduct newer studies to know the safety of the method before it can used in human clinical trials.
Monoclonal Antibody Therapy for Alzheimer's Disease
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies to bind specific targets, such as cells or proteins. Its main purpose is to induce the immune system to attack specific targets.
In Alzheimer's disease, the method intends to use the immune cells to remove the corrupted beta-amyloid protein in the brain. Unfortunately, the results mostly led to failure because of certain factors including:
- Inconsistency of the immune response to remove the accumulation of the corrupted protein.
- Lack of immune response in certain patients that ultimately resulted in the failure of the therapy.
- Adverse effects of therapy and immune response of the patient.
- Expensive cost due to repeated administrations to become effective.
While the cure for Alzheimer's disease remains unavailable, the recent study at Washington University may pave the way to the development of the first immunotherapy for the crippling disorder.
[메디컬리포트=Ralph Chen 기자]