Immunization against Alzheimer's
Researchers from the University of Kansas used a recombinant methionine-saturated (Met) protein obtained from corn, which was then oxidized in vitro to produce an antigen – saturated methionine sulfoxide (MetO) protein. This antigen prompts the immune system to produce antibodies against the MetO component of beta-amyloid, a protein that is toxic to brain cells and accumulates in Alzheimer's disease.
With age, oxidative stress increases in the body, and then beta-amyloid and other toxic proteins accumulate, oxidize and aggregate; these proteins are resistant to degradation or excretion. The author of this work, Jacob Moskowitz, in a 2011 study injected mouse models of Alzheimer's disease with a similar protein saturated with methionine sulfoxide, and demonstrated an approximately 30% decrease in amyloid plaques in the hippocampus - the area of the brain in which the most severe damage is noted in Alzheimer's disease.
The MetO antigen used by Moskowitz in a new study to vaccinate mouse models of Alzheimer's disease can induce the immune system to produce antibodies against MetO-containing proteins, including beta-amyloid, and, ultimately, reduce the levels of toxic forms of beta-amyloid and other possible proteins in the brain.
Moskowitz and his colleagues injected the MetO antigen into 4-month-old mice that had been genetically modified to develop a familial form of Alzheimer's disease. This treatment induced the production of antibodies against MetO in plasma, which remained in the blood of animals until at least 10 months of age.
In a series of tests, the researchers evaluated the short-term memory of immunized and control mice using a Y-shaped maze. This is a very important test, because with Alzheimer's disease, people lose short-term memory, while old memories are preserved. The researchers placed each mouse in a maze with a fork so that it could walk either on the left or on the right tunnel. After that, a third tunnel was introduced in the middle, and if the mouse considers it new, it will, due to natural curiosity, spend more time exploring this new road. If the mouse does not even notice the appearance of a new tunnel, because it forgets about it almost immediately after seeing it, it will spend more time on the right or left tracks.
According to Moskowitz, in mice injected with methionine sulfoxide-rich protein, memory improved by about 50% compared to the control.
In another experiment, mice had to find a platform in a water maze. The researchers trained mice for six days, and even those with Alzheimer's disease eventually identified the location of the platform, but after the second day it became obvious that immunized mice learn much faster than non-immunized ones. Then the platform was removed to check if the animals remembered where it was. Again, the researchers saw a difference: immunized mice spent more time near the area where there was a platform on which they trained, compared with non-immunized mice.
In addition to improving short-term memory, mice injected with the antigen had better long-term memory, lower levels of beta-amyloid in both blood plasma and brain, especially in the astrocytes of the hippocampus and cerebral cortex, a lower percentage of activated microglia and increased antioxidant abilities in the same areas of the brain.
Based on the results obtained, the researchers suggest that active immunization can delay or prevent the onset of Alzheimer's disease in humans. It will be more effective than passive immunization protocols, since the MetO antigen stimulates the immune system to produce its own antibodies. With passive immunization, ready-made antibodies are injected into the body, and this carries the risk of serious toxic side effects, as well as rejection by the own immune system.
The next steps of researchers in this direction will be conducting preclinical trials and clinical studies.
Article by A.S.Smith et al. Protective Effects against the Development of Alzheimer's Disease in an Animal Model through Active Immunization with Methionine-Sulfoxide Rich Protein Antigen is published in the journal Antioxidants.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Kansas: Study preserves memory in mice, offering promising new basis for active immunization against Alzheimer's disease.