Researchers have discovered the mechanism that inhibits the development of Alzheimer's

Researchers from Tel Aviv University discovered why an environment rich in physical and mental stimulation can slow down the development of Alzheimer's disease, and express hope to develop a drug to treat the disease

The mechanism that inhibits the development of Alzheimer's

From studies done in the past, it is known that challenging mental and physical activity may slow down the development of Alzheimer's disease, but now researchers from Tel Aviv University, in collaboration with Bar-Ilan University, have found the biological mechanism that may explain how exactly this happens. The study, recently published in the journal Translational Psychiatry, was carried out by Dr. Boaz Barak, and was conducted in the laboratory of Prof. Uri Ashari from the Department of Neurobiology in the Faculty of Life Sciences and the Segol School of Neuroscience at Tel Aviv University, in collaboration with the laboratories of Dr. Noam Shomron and Prof. Daniel Michaelson, also from Tel Aviv University, and Dr. Eitan Okon from Bar-Ilan University.

Protein increases

Alzheimer's disease mostly affects people over the age of 65 and is accompanied by degeneration of brain cells and memory loss. Beyond the fact that it is an incurable disease that imposes a heavy burden on the patient's family, at the biological level the disease is characterized by a decrease in the amount of proteins responsible for the communication process between nerve cells in the brain - which leads to impairment of the patient's cognitive and physical abilities. However, over the years it became clear that the level of these proteins increases significantly following exposure to an environment rich in stimuli. As part of the study, the researchers compared the amount of microRNA (microRNA), the molecule responsible for controlling the level of proteins in the cell, in healthy mice and in model mice for Alzheimer's disease - that is, mice that were genetically engineered to develop the disease together for the purpose of the experiment.

Initially, the team of researchers compared the amount of microRNA sequences in healthy mice raised in an environment enriched with cognitive and physical stimuli, with that of healthy mice raised in a normal breeding environment. In a second step, the researchers compared the amount of microRNA sequences in Alzheimer's model mice that were raised in a normal breeding environment, to that of healthy mice of the same age that were raised in a similar environment. In the last step, it was checked if there are microRNA sequences that increased as a result of Alzheimer's disease on the one hand, and decreased as a result of exposure to an enriched environment on the other hand (reversed change).

"The same microRNA sequences that were found to change in a reverse manner following Alzheimer's and exposure to an enriched environment were also found to be responsible for the expression of the same proteins that affect the communication between the nerve cells in the brain," says Dr. Barak. "The expression of those sequences in the cell increased as a result of exposure to Alzheimer's disease - and therefore led to a decrease in the amount of proteins that could damage neural activity in the brain. On the other hand, the exposure to the enriched environment showed a decrease in the expression of microRNA sequences, resulting in an increase in the amount of proteins, which may lead to an improvement in neural activity in the brain."

Forget about Alzheimer's in the future

In addition, the research team discovered a number of microRNA sequences that underwent a quantitative change in the very early stages of the disease, so that in the future they could be used for early detection of the disease - perhaps even with a simple blood test. "These sequences were unknown to science, and they are of crucial importance for understanding the first stages of the disease at the cellular level. Studies conducted in recent years show that it is possible to isolate and quantify the level of expression of various microRNA sequences in a normal blood test, and I hope that in the coming years it will be possible to detect such changes in the brain itself and not only in the blood," says Dr. Barak.

In Barak's estimation, it is possible that the research findings will be used to adjust specific treatment for each patient according to the rate of progression of his disease, as well as to actually delay damage to neural activity by increasing or decreasing the expression of the microRNA sequences, as required.

According to Prof. Ashari, it is known today that mental exercises and fitness exercises improve the condition of Alzheimer's patients. Those microRNA sequences, which in this case were tested in laboratory mice that are a model for Alzheimer's disease, not only improve the condition of the patients but also function like cellular control switches that activate a whole group of proteins that are responsible for many vital cellular functions. The findings of the current study make it possible to study the disease in a more specific way and improve the researchers' ability to develop a target-oriented medicine.