Researchers from Laval University in Quebec City and the University of Lethbridge in Alberta say they were able to not only slow the progression of the disease, but also reverse some of the cognitive symptoms associated with Alzheimer’s in an animal model.
Although this remains to be demonstrated in humans, we believe that the mechanism we have highlighted is a very interesting therapeutic target as it is not limited to halting disease progression, but also partially improves some cognitive functions. Also makes it possible to restore from .
Alzheimer’s is the most common cause of dementia. There is currently no effective treatment for this disease, which affects 50 million people worldwide. On the other hand, as the world’s population continues to age, it is projected that the number of people with dementia will triple to 152 million by the year 2050.
At least 564,000 Canadians in Canada are suffering from this incurable disease. According to the Alzheimer’s Society of Canada, in 15 years this number will increase to 937,000 affected people.
case of disturbed neurons
Previous studies have shown that even before symptoms of Alzheimer’s appear, brain activity is disrupted in people who will develop the disease. Researcher De Koninck explained that there is neuronal hyperactivity and disorganization of certain signals in the brain.
The researchers’ hypothesis is that a mechanism that regulates neuronal activity, more precisely the mechanism that is responsible for inhibiting neuronal signals, is disturbed.
According to statistics from the Quebec Alzheimer’s Society, in the coming years, the number of people affected by neurocognitive disorders, primarily Alzheimer’s disease, will increase by 65%. About one million Canadians would be affected. Most Alzheimer’s patients are under the age of 60.
Photo: Associated Press/Matt York
The main inhibitor of nerve signals in the human brain is the GABA neurotransmitter, which works in close cooperation with a cotransporter, KCC2.
It is an ion pump located in the cell membrane, which circulates chloride ions and potassium ions between the inside and outside of neurons.
Professor de Koninck explained.
Placing an ion pump located in the cell membrane of neurons would slow or reverse the progression of the disease.
When KCC2 is lost from the cell membrane, it can lead to neuronal hyperactivity. One study already showed that people who died of Alzheimer’s disease had reduced levels of KCC2 in their brains. This gave us the idea to investigate the role of KCC2 inhibitor in animal models of Alzheimer’s disease.
Thus, the scientists used a series of mice that showed signs of Alzheimer’s disease when they reached the age of four months, with KCC2 in two areas of their brain, the hippocampus and the prefrontal cortex. The level decreased.
In humans, KCC2 inhibitors also decreased these two areas in people with the disease.
This discovery led the researchers to develop a molecule that activates KCC2. When this molecule was given to experimental rats, their spatial memory and social behavior improved.
In the long term, the molecule also protected them from decreased cognitive abilities and neural hyperactivity.
Our results do not indicate that loss of KCC2 causes Alzheimer’s disease. On the other hand, its absence causes an ionic imbalance which leads to neuronal hyperactivity which can lead to the death of neurons. This suggests that preventing KCC2 loss may delay and possibly even reverse some disease manifestations.
Unfortunately, the molecule, called CLP290, cannot be used in humans. Professor de Koninck’s team is looking for other molecules that people with Alzheimer’s disease can tolerate.
The results of the research were published in the scientific journal Brain, Cerebro.
Source: RC/PC
Adaptation: RCI / R Valencia