Friday, October 07, 2022

42 previously unknown genes for Alzheimer’s disease discovered

“Lifestyle factors such as smoking, exercise, and diet influence our development of Alzheimer’s, and working to address these now is a positive way to reduce risk,” he said. “However, 60-80% disease risk is based on our genetics 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 point to additional pathways for disease progression other than the well-known APOE e4 gene or the development of amyloid beta and tau, two hallmark proteins that build up in the brain with devastating consequences as Alzheimer’s progresses.

“Creating a comprehensive list of Alzheimer’s disease risk genes is like putting together the pieces at the edge of a puzzle, and although this work doesn’t give us the full picture, it does provide a valuable framework for future development,” Susan Koolhaas, director of research at Alzheimer’s Research UK, who was not involved in the research.

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

“The new risk types identified in the current study are significantly associated with Alzheimer’s disease,” said the study, published Monday in the journal 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 the deadly brain disease.

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

“This paper gives us more tools in our toolbox to eventually target Alzheimer’s disease more precisely,” said Isaacson, who was not involved in the study.

path to new disease

The global study analyzed the genomes of 111,326 people with clinically diagnosed Alzheimer’s and compared them with the genes of 677,663 cognitively healthy people. The genomes were supplied by clinics in more than 15 members of the European Union, Argentina, Australia, Brazil, Canada, Iceland, Nigeria, New Zealand, the UK and the United States.

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The study identified 75 genes that are associated with an increased risk of Alzheimer’s, 33 of which were already known. It also confirmed years of research into the roles of amyloid beta and tau.

Many of the 42 new genes found to be associated with Alzheimer’s appear to be involved in several suspected but unconfirmed pathways for the development of the disease. One such pathway is the body’s immune system, which is designed to protect us from germ invaders.

Several genes were linked to an immune regulator called LUBAC, which the body needs to activate genes and prevent cell death. The study also found that microglia, immune cells in the brain that are tasked with “taking out the garbage” — clearing away damaged neurons — play an important role in people with diagnosed Alzheimer’s disease.

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

Another important pathway, according to the study, involves genes associated with 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 protein in the study was tumor necrosis factor alpha, which is made by the immune system to control inflammation. The study found a group of genes associated with TNF, as it is called. Although the chemical’s actual role is to mobilize the body’s defenses for a fight, it is also a culprit in many autoimmune diseases in which the body alters itself, such as rheumatoid and psoriatic arthritis, Crohn’s disease, and type 1 diabetes.

The study found additional complex gene interactions, Isaacson said, all of which suggest that “Alzheimer’s disease is a multifactorial disease, made up of different pathologies, and each individual has its own roadblocks.”

“Clinicians always say, ‘Once you’ve seen a person with Alzheimer’s, you’ve seen a person with Alzheimer’s. The disease presents differently and progresses differently in different people.”

One common reason?

Another important insight of the study was that brain disorders such as Parkinson’s, frontotemporal dementia, Lewy body disease and amyotrophic lateral sclerosis may have the same underlying genetic basis: “Taken as a whole, these data are thus associated with neurodegenerative diseases.” may emphasize a potential continuum,” the study said.

“The scientific and medical community view neurodegenerative disease processes as very distinct and distinct, and that is how we have been studying them for a long time,” said Dr. Kellian Neotis, a neurologist specializing in the prevention of Alzheimer’s and Parkinson’s disease at Weill Cornell Medicine. and New York-Presbyterian.

“This emphasizes that there may be a larger continuum between these disease processes than we really understood before,” said Neotis, who was not involved in the study.

“Young people may have similar underlying genetic risks, and they can cause Parkinson’s in one person and Alzheimer’s in another,” she said. “Actually, it’s less relevant. It’s important to understand that this is what’s going wrong with their bodies, so let’s start early and target this pathway.”

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By generating this more complete picture of genetic risk—which needs to be overcome and defined in future studies—the study authors also developed “a new scoring system for predicting Alzheimer’s disease risk,” Tara Spiers-Jones. , deputy director of the Center for Discovery Brain Sciences at the University of Edinburgh, said in a statement.

“The tool will be useful to researchers, but it will soon be used for people not participating in clinical trials,” said Spiers-Jones, who was not involved in the study.

Physician researchers like Isaacson and Neotis know that a device like this is exactly what patients want who are concerned about their brain health.

“People want to know, ‘What are my chances?’ And then ‘What can I do about it?’ Isaacson said. “Not today, but in the near future, we will be able to calculate the likelihood of developing Alzheimer’s or any other brain disorder in a more accurate way, and this will help with precise medicine and lifestyle management.”

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