08 December 2017

Mice without Alzheimer's disease

Scientists: gene blocking protected mice from developing Alzheimer's disease

RIA News

Suppression of the APOE gene associated with Alzheimer's disease protected mice from memory loss and further destruction of nervous tissue, doctors say in an article published in the journal Neuron (Huynh et al., Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis).

"Our colleagues have long been interested in the role of APOE in the development of the disease, but in recent years they have conducted very few experiments in which they tried to suppress its work. We have shown that APOE is not just involved in the development of Alzheimer's disease, but that it can be used as a "target" for its treatment," said David Holtzman from Washington University in St. Louis (USA).

The APOE gene and protein are some of the most important molecules in brain cells and other parts of the body related to the metabolism and circulation of cholesterol and fatty acids in the body. Mutations in this gene, as recent genetic studies show, are associated with the development of Alzheimer's disease, atherosclerosis and some other diseases.

For example, the APOE4 mutation, which is present in the genome of about 10% of the world's inhabitants, increases the likelihood of developing Alzheimer's disease three times. The presence of such a mutation in two copies of APOE increases the chances of acquiring this disease by 12 times and makes the onset of Alzheimer's disease almost inevitable.

Holtzman and his colleagues discovered a new way to fight Alzheimer's disease by observing the work of brain cells of mice that were carriers of two copies of APOE4. These mutations, as scientists believe today, accelerate the accumulation of "protein debris" in the neurons of the brain and cause it to unite into beta-amyloid plaques that interfere with the normal work and life of nerve cells and gradually kill them.

The scientists decided to test what would happen if the gene was blocked by using special short DNA molecules that prevent the cell from reading this part of the genome and producing APOE protein molecules. After growing several dozen mice, the scientists divided them into two groups and began to regularly inject large doses of these molecules into their bodies.

Half of the mice, as Holtzman says, received such injections from the first day of their lives, when they did not suffer from Alzheimer's disease, and the rest of their relatives – only four months later, when a sufficient amount of "protein garbage" had already accumulated in their brains.

As this experiment has shown, blocking the work of APOE does prevent the development of Alzheimer's disease, but it only works if this procedure is started before its visible traces appear.

This was expressed in the fact that the brains of mice who received injections of medication from the beginning of life did not contain large accumulations of "protein debris" even at the 8th month of life, whereas their relatives from the second group continued to suffer from Alzheimer's disease even after blocking APOE.


Amyloid plaques on the brain slices of the experimental mouse (above) and the mouse from the control group. A snapshot of Tien-Phat Huynh from Alzheimer's damage in mice reduced with compound that targets APOE gene – VM.

On the other hand, the drug was still able to slow down the development of the disease and protect mice from the most unpleasant consequences of its appearance in both cases.

This fact, according to doctors, suggests that APOE plays a key role in the early stages of the development of the disease, and subsequent changes in the work of brain neurons are already associated with other proteins and DNA sites.

"Blocking APOE stops the development of Alzheimer's disease only if we start it before the first protein plaques appear. On the other hand, even if they have arisen, such therapy reduces the harm they cause to brain cells. It remains to figure out how to create a drug that can do the same and not interfere with the work of other parts of the body," concludes Holtzman.

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