42 previously unknown genes for Alzheimer’s disease discovered

“Lifestyle factors such as smoking, exercise and diet influence the development of our Alzheimer’s disease, and working to address them now is a positive way to reduce our risk,” he added. “However, 60-80% of the risk of disease depends on our genes and so we must continue to look for biological causes and develop much-needed treatments for the millions of people affected worldwide.”

Previously unknown genes suggest additional pathways for disease progression beyond the well-known APOE e4 gene or the development of amyloid beta and tau proteins, two distinct proteins that accumulate in the brain with devastating results as Alzheimer’s disease progresses.

“Creating an extensive list of genes that cause Alzheimer’s risk is like putting the pieces of a puzzle together, and while this work doesn’t give us a complete picture, it does provide a valuable framework for future developments,” said Susan Koolhaas, MD. , director. From research by Alzheimer’s Research UK, which was not involved in the research.

The study found that several newly discovered genes focus on the highly detailed interactions between proteins in the body that control how inflammation and the immune system damage brain cells.

“The new risk variables identified in the current study are significantly associated with progression” of Alzheimer’s disease, the study says. Published Monday in Nature Genetics.

Experts say the discovery will provide scientists with potential new targets for treatments, drugs and lifestyle changes that could reduce the risk of fatal brain diseases.

“The future of Alzheimer’s disease is precision medicine and prevention,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at the Brain Health Center at Florida Atlantic University’s Schmidt School of Medicine.

“This article gives us a lot of tools in our toolbox that, in the end, more precisely target Alzheimer’s disease,” said Isaacson, who was not involved in the study.

New disease pathways

The global study analyzed the genomes of 111,326 people with clinically diagnosed Alzheimer’s disease and compared those with genes from 677,663 cognitively healthy people. The genome has been made available by clinics in more than 15 EU member states, 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 disease, 33 of which were already known. Years of research have also confirmed the role of amyloid beta and tau.

Of the 42 new genes found to be associated with Alzheimer’s disease, many clustered in several suspected but uncertain pathways for the disease’s progression. One such pathway is the body’s immune system, designed to protect us from invading germs.

Several genes have been linked to an immune regulator called LUBAC, which the body needs to turn genes on and prevent cell death. The study also found that microglia, the brain’s immune cells tasked with “taking out the trash” – removing damaged neurons – play an important role in people with Alzheimer’s disease.

Some of the newly discovered genes may make microglia less efficient, “which can accelerate the disease,” Williams said.

Another important pathway, according to the study, involves genes linked to inflammation. The body uses inflammation as a defense mechanism to kill pathogens, but it also plays a role in removing damaged cells.

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One of the proteins that stood out in the study was tumor necrosis factor-alpha, which is made by the immune system to regulate inflammation. The study found a group of genes linked to TNF, as it is called. While the chemical’s real role is to mount the body’s defenses to fight, it is also a causative agent of many autoimmune diseases in which the body turns against itself, such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, and type 1 diabetes. .

Additional complex genetic interactions were found throughout the study, which makes it clear that “Alzheimer’s is a multifactorial disease, made up of different diseases, and each has its own path,” Isaacson said.

“Doctors always say, ‘Once you see someone with Alzheimer’s, you see someone with Alzheimer’s,’” he said.

common cause?

The other main insight from the study was that brain disorders such as Parkinson’s disease, frontotemporal dementia, Lewy body disease, and amyotrophic lateral sclerosis may have the same underlying genetic basis: “Overall, these data may emphasize the potential continuity between neurodegenerative diseases.” , said the study.

Kilian Newtis, a neurologist specializing in the prevention of Alzheimer’s and Parkinson’s disease at Weill Cornell Medicine and New York Presbyterian, said.

“This confirms that there may be greater communication between these disease processes than we previously understood,” said Newtis, who was not involved in the study.

“Young people can have a similar underlying genetic risk and can lead to Parkinson’s disease in one person and Alzheimer’s disease in another,” she said. “Actually, it’s less important. What’s important is understanding that this is what’s going wrong with their bodies, so let’s start early and head down that path.”

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In creating this more complete picture of genetic risk – which must be clarified and identified in future studies – the study authors also developed a “new scoring system to predict Alzheimer’s risk”, Tara Spears-Jones, deputy director of the University Edinburgh University of Brain Sciences. Discovery Center said in a statement.

“This tool will be useful to researchers, but it probably won’t be used anytime soon for people who are not participating in clinical trials,” said Spiers-Jones, who was not involved in the study.

Clinical researchers like Isaacson and Niotis know that a tool like this is exactly what brain-health-conscious patients want.

People want to know ‘What are my chances?’ So, “What can I do about it?” said Isaacson. “Not today, but in the near future, we will be able to calculate a person’s likelihood of developing Alzheimer’s disease or another brain disorder in a more accurate way, and that will help with medical care and lifestyle management.”

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