“This is a landmark study in Alzheimer’s research and the culmination of 30 years of work,” said Julie Williams, co-author of the study, director of the study at Cardiff University’s UK Dementia Research Institute in the UK.
“Lifestyle factors such as smoking, exercise and diet affect the development of our Alzheimer’s, and now working to address them is a positive way to reduce our own risk,” he added. “However, 60-80% of the risk of disease is based on our genetics and so we must continue to search for biological causes and develop much needed treatments for millions of infected people worldwide.”
Previously unknown genes point to the development of the well-known APOE e4 gene or amyloid beta and Tau, as well as additional pathways to disease progression, two Hallmark proteins that are produced in the brain with devastating consequences as Alzheimer’s progresses.
“Creating a comprehensive list of Alzheimer’s disease risk genes is like assembling the pieces of a puzzle, and although this task does not give us a complete picture, it provides a valuable framework for future development,” said Susan Kohlhaus, director of Alzheimer’s Research UK. Who was not involved in the study.
Studies have shown that a number of newly discovered genes focus on the body’s very detailed response to proteins that control how inflammation and the immune system can damage brain cells.
A study published Monday in the journal Nature Genetics states that “the new risk factors identified in the current study are significantly associated with the progression of Alzheimer’s disease.”
The discovery could provide scientists with new potential targets for treatment, medication and lifestyle changes that could reduce the risk of fatal brain disease, experts say.
“The future of Alzheimer’s disease lies in specific drugs and prevention,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at the Schmidt College of Medicine Brain Health Center at Florida Atlantic University.
“This paper gives us many more tools in our toolbox, ultimately, more specifically on Alzheimer’s disease targets,” said Isaacson, who was not involved in the study.
The path to new diseases
The global study analyzed the genomes of 111,326 people, including clinically diagnosed Alzheimer’s, and compared the genes of 677,663 cognitively healthy people. Genomes were provided by clinics from more than 15 member states in the European Union, Argentina, Australia, Brazil, Canada, Iceland, Nigeria, New Zealand, the United Kingdom and the United States.
The study identified 75 genes associated with an increased risk of Alzheimer’s, 33 of which were already known. This confirms years of research into the role of amyloid beta and tau.
Forty-two new genes have been found to be linked to Alzheimer’s, a number of suspicious but unproven pathways to the development of many diseases. One such pathway is the body’s immune system, which is designed to protect us from bacterial invaders.
Many genes are linked to an immune regulator called LUBAC, which is needed to activate the body’s genes and prevent cell death. Studies have also shown that the microglia, the brain’s immune cells, are responsible for “expelling waste” – which is responsible for cleaning up damaged neurons – to play a key role in people diagnosed with Alzheimer’s disease.
Some newly discovered gene microglia may be less effective, “which could accelerate the disease,” Williams said.
Another key pathway, according to research, involves genes associated with inflammation. The body uses inflammation as a defense to kill germs, but it also plays a role in removing damaged cells.
One protein that has been studied is tumor necrosis factor alpha, which is produced by the immune system to control inflammation. The study found a cluster of genes associated with TNF, called. Although the chemical’s main role is to mobilize the body’s immune system to fight, it is also a culprit for many autoimmune diseases where the body returns to itself, such as rheumatoid and psoriatic arthritis, Crohn’s disease and type 1 diabetes.
Studies have found additional complex gene interactions, all of which explain that “Alzheimer’s disease is a multifactorial disease, composed of different pathologies, and each person has their own path,” Isaacson said.
“Doctors always say, ‘Once you see someone with Alzheimer’s, you see someone with Alzheimer’s.’ The disease is presented differently and progresses differently among different people, ”he said.
A common cause?
Another key insight into the study was that brain disorders such as Parkinson’s, frontotemporal dementia, leukemia, and amyotrophic lateral sclerosis may have the same underlying genetic basis:
“The scientific and medical communities view the processes of neurodegenerative diseases as very different and distinct, and as such we have been studying them for a long time,” said Dr. Kellyn Neotis, a neurologist and New York-Presbyterian who specializes in Alzheimer’s and Parkinson’s disease prevention.
“It emphasizes that there may be a greater continuity between these disease processes than we previously understood,” said Neotis, who was not involved in the study.
“Young people may have a similar underlying genetic risk, and they may have Parkinson’s in one and Alzheimer’s in the other,” he said. “In reality, it is less relevant. The important thing is to understand that this is what is going wrong with their body, so let’s get started and notice this path. “
To create this more complete picture of genetic risk – which needs to be explored and defined in future research – the study authors also developed a “new scoring system for predicting Alzheimer’s disease risk”, said Tara Spire-Jones, deputy director at the University of Edinburgh’s Center for Discovery Said in a statement.
“This tool will be useful for researchers but will not be used soon for those who are not participating in clinical trials,” said Spire-Jones, who was not involved in the study.
Clinical researchers like Isaacson and Neotis know that there is a tool that patients want if they are concerned about the health of their brain.
“People want to know, ‘What are my chances?’ And then ‘What can I do about it?’ “Isaacson says. “Not today, but in the near future, we will be able to more accurately calculate a person’s risk of developing Alzheimer’s or other brain disorders, and this will help in accurate treatment and lifestyle management.”
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