Destroy plaques
Alzheimer's disease begins long before the appearance of clinical signs. Amyloid plaques that damage brain tissue are considered the main pathogenetic factor of the disease. Researchers agree that the fight against these plaques will help stop the progression of the disease or even completely cure the patient.
Plaques that accumulate in Alzheimer's disease consist mainly of the pathological protein beta-amyloid. But inside them, a small amount contains another protein – apolipoprotein E (APOE). A group of researchers from the University of Washington, led by David Holtzman, demonstrated a strategy for combating plaques using antibodies targeting the APOE protein.
Amyloid plaques that destroy the brain are formed over the years. Therefore, it is quite difficult to get rid of them, especially in the advanced stages of the disease. As the researchers write, it is desirable to start treatment with the method described by them even in the preclinical stage. In addition, the less plaques come into contact with brain tissue, the fewer irreversible changes will occur and the higher the chance of recovery.
Scientists have proposed using antibodies that recognize and bind the APOE protein. The resulting antibody-APOE complex attracts immune cells, they begin to destroy it. In the process, not only APOE is destroyed, but also the beta-amyloid located nearby.
Antibodies to APOE (red) bind to amyloid plaques (blue).
To confirm their hypothesis in vivo, the authors replaced the APOE coding genes in mice with a human analogue. For six weeks, they were given a placebo or antibodies to APOE once a week. After the course of therapy, the number of plaques in the brain was determined. In this way, several types of antibodies were tested.
As a result, the antibody HAE-4 was selected. Its introduction led to a reduction in the number of amyloid plaques by 50%, while the level of APOE protein in the blood did not change in any way. APOE plays an important role in the transport of lipids and cholesterol, therefore, a decrease in its level in the blood during treatment would lead to the development of serious side effects in the form of metabolic disorders.
The HAE-4 antibody effectively bound to APOE in the brain and did not react in any way to APOE circulating in the blood due to the special structure of the protein in the plaque.
Many laboratories around the world are trying to use antibodies as a treatment for Alzheimer's disease. But the problem is that no method in which antibodies target beta-amyloid has proven its safety: the risk of complications in the form of inflammation or swelling of the brain is too high.
Antibodies targeting APOE can be an effective treatment with a lower risk of complications in the form of an immune system reaction. The fact is that beta-amyloid accumulates much more than APOE, so anti-APOE can have a more gentle effect than anti-amyloid antibodies.
Studies on the safety and efficacy of APOE antibodies will continue.
Article by F. Liao et al. Targeting of non-lipidated, aggregated apoE with antibodies inhibits amyloid accumulation will be published in the Journal of Clinical Investigation.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on WUSTL materials: Antibody removes Alzheimer's plaques, in mice.