One step closer to an Alzheimer's treatment... New gene discovery offers a glimmer of hope for clinical research!

Led by Prof. Dr. Richard Mayeux, Prof. Dr. Badri Vardarajan, and Prof. Dr. Çağhan Kızıl from Columbia University in the USA, a study has revealed a genetic variation that reduces the risk of Alzheimer's by 71 percent, as well as the mechanism behind this effect.

Turkish scientist Prof. Dr. Çağhan Kızıl, who is part of the team, stated that the study aimed to understand the genetic basis of Alzheimer's, saying, "In our study conducted on 11,000 people from various populations and ethnic groups, we performed whole-genome sequencing from blood samples and looked at genetic changes. We conducted this study specifically on individuals with high genetic risk factors for Alzheimer's, and we asked the question, 'Are there other protective genetic traits in those who do not have Alzheimer's?' We found that the gene we identified and a small change within it provide this protection."

ONE PERSON IS DIAGNOSED WITH ALZHEIMER'S EVERY 4 SECONDS

According to a report by Sibel Bahçetepe from BirGün; a recent study conducted at Columbia University on Alzheimer's, one of the most common types of dementia, has caused excitement in the scientific world with the discovery of a gene that provides a significant 71 percent protection against Alzheimer's.

Explaining the study to BirGün, Kızıl said that Alzheimer's, which accounts for 70 percent of dementia cases, is an increasingly growing health problem. Explaining that nearly 50 million people are living with Alzheimer's according to the World Health Organization (WHO), Kızıl said, "We know that Alzheimer's will increase as average life expectancy rises. Projections for 2050 suggest that the number of patients will exceed 100 million. One person is diagnosed with Alzheimer's every 4 seconds."

Regarding the gene study that found a 71 percent reduction in Alzheimer's risk, Kızıl provided the following information: "This study is a genetic epidemiology study focused on understanding the prevalence and foundation of the disease in society. It is a joint project of three laboratories. It began as a study investigating the genetic basis of Alzheimer's, aiming to understand the genetic changes that lead to Alzheimer's in various populations and ethnicities. Blood samples were taken from various people and populations, and their genome sequences were examined."

"WE SEE THAT PEOPLE IN THE RISK GROUP DO NOT DEVELOP ALZHEIMER'S"

Explaining that they approached the study from a different perspective, Çağhan Kızıl said, "We know there are certain genetic changes that lead to Alzheimer's or increase the risk of the disease. If you have two copies of some changes in your DNA, it almost guarantees you will develop Alzheimer's by the time you are 70-80 years old. However, very interestingly, we see that some people with this genetic risk do not develop Alzheimer's, even though we expect them to. They are, in a way, resistant to the disease. We asked the question, 'Could these people have developed a protective mechanism within themselves, even though they are few in number?' The gene we found and a change within it gave us a 'yes' to this question."

ZEBRAFISH MODEL

Explaining that the zebrafish was also used in the research, Kızıl said, "The zebrafish is a vertebrate and is genetically very close to humans. To test our findings experimentally, we worked with our Alzheimer's model in zebrafish. Experiments on zebrafish models showed how the level of fibronectin facilitates the clearance of amyloid plaques that cause Alzheimer's disease. The fibronectin gene also exists in zebrafish, and just like in humans, it is found around blood vessels. We asked the question, 'If we block the activity of the gene, can we reduce Alzheimer's?' and we removed this gene from the fish genome. As a result, we saw that the clearance of pathological factors associated with Alzheimer's from the brain increased, the death of nerve cells decreased, and the brain protected itself better. This finding tells us why the genetic variation we discovered protects human brains from Alzheimer's."

HOPE FOR TREATMENT DEVELOPMENT

Explaining that it is known there are some protective factors in Alzheimer's, Dr. Çağhan Kızıl said, "Most of us know about the plaques in the brain that create Alzheimer's. The idea that 'if we stop the mechanism that creates those plaques, we can prevent plaque formation and prevent Alzheimer's' has been known for a long time. However, our perspective was a bit different. This gene we found is not about the formation of Alzheimer's, but actually about developing resistance to it and standing against it." Stating that the development of Alzheimer's takes place over 20-30 years, Kızıl summarized the following: "During this process, plaques and other proteins gradually accumulate. These need to be cleared from the brain. The more effectively we can clear them, the more we delay the onset of Alzheimer's, and therefore, we provide protection. In fact, the protein we found is a protein that negatively affects this plaque formation process and the process of plaque accumulation and clearance; that is, it slows it down. The genetic change we found renders this protein ineffective. Or we can say it reduces its effect slightly, so we are setting a barrier in front of a mechanism that creates Alzheimer's or makes it even more severe. This naturally exists in some people. We can call them lucky people; they can protect themselves against Alzheimer's. We believe that by learning the protective mechanisms against Alzheimer's, a treatment can be developed against this frightening disease."

"IT GIVES HOPE"

Kızıl noted the following:

"The research showed that a specific mutation in the fibronectin gene can significantly reduce the risk of Alzheimer's. Fibronectin is part of the protective layer around the blood-brain barrier. Normally, in Alzheimer's patients, excessive fibronectin accumulates in this barrier, contributing to the progression of the disease. The discovered genetic variation prevents this excessive accumulation, thereby protecting brain cells. When there is too much fibronectin, clearance cannot be done effectively. The protective variation makes brain clearance more effective at this point and also reduces other pathological processes in the brain, thus providing protection against Alzheimer's. Since the study states that protection against Alzheimer's is possible, it gives hope for clinical research."

News Source: 12punto