Dementia: Over 75 genes linked to risk of Alzheimer’s disease in ‘landmark’ new study

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The number of people living with dementia is rising exponentially as people age. The figures make for dispiriting reading but progress is afoot in understanding the risk factors. A major new study, published in the journal Nature Genetics, has identified the main risk genes linked to Alzheimer’s disease, which affects memory, thinking and behaviour.

This new insight about the genetic risk of Alzheimer’s is the largest study of its kind, the researchers have said.

According to the “landmark” study, the findings indicate new avenues for treatment in a disease that currently has no cure.

Researchers said that in the future, genetic testing may help to identify people who are most at risk of developing the condition before symptoms start to appear.

What did they find out?

The new study identified 75 genes linked to a greater risk of developing Alzheimer’s, including 42 new genes not previously implicated in the condition.

Doctor Rebecca Sims, senior research fellow at Cardiff University and UK Dementia Research Institute co-investigator – and co-leader of the study, said: “This study more than doubles the number of identified genes influencing risk for the more common form of Alzheimer’s disease.

“It provides exciting new targets for therapeutic intervention and advances our ability to develop algorithms to predict who will develop Alzheimer’s in later life.

“As well as confirming previous findings relating to certain proteins that build up in and around nerve cells as Alzheimer’s disease progresses, the study provides evidence to support a role for inflammation and the immune system in the disease.”

Professor Julie Williams, centre director at the UK Dementia Research Institute at Cardiff University – co-author of the study and leader of the Genetic and Environmental Risk for Alzheimer’s disease consortium, said: “This is a landmark study in the field of Alzheimer’s research and is the culmination of 30 years’ work.

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“Genetics has and will continue to help us identify specific disease mechanisms which we can target therapeutically.

“This piece of work is a major leap forward in our mission to understand Alzheimer’s, and ultimately produce several treatments needed to delay or prevent the disease.”

The largest study of its kind involved researchers analysing the genome – complete set of genetic information – of more than 100,000 people with Alzheimer’s disease and comparing them with over 600,000 healthy individuals to look for differences in their genetic makeup.

The next step towards finding treatments for Alzheimer’s is for researchers to focus on the specific risk genes identified in this study and closely examine their role in the dysfunction and death of brain cells.

Based on the results, the researchers also devised a scale to determine how likely it is that patients with cognitive impairment will go on to develop Alzheimer’s disease within three years.

This is not currently intended for use, but researchers hope it will improve the evaluation of new drugs in clinical trials.

In future, the scientists hope the findings can be used to identify people within the population who are at greatest risk of developing Alzheimer’s disease before they start to develop the condition.

Commenting on the findings, Doctor Susan Kohlhaas, Director of Research at Alzheimer’s Research UK said: “Genes are the instruction manual for life, the code for producing proteins that govern our biology. Certain gene variations can predispose someone to disease, including Alzheimer’s, however they aren’t the only factor, with age and other lifestyle factors accounting for some of the risk.

“Previous genetic discoveries underpin much of our current understanding of Alzheimer’s disease and the direction of research into new treatments. Creating an extensive list of Alzheimer’s disease risk genes is like having the edge pieces of a puzzle put together, and while this work doesn’t give us the full picture, it provides a valuable framework for future developments.

“Using this genomic wide sequencing approach, researchers were able to uncover more evidence that the immune system plays a pivotal role in the development of Alzheimer’s, which gives us clues about the pathways that might be most important to look at in our search for new treatments. The research also, however, tells us just how complex Alzheimer’s is, with several different mechanisms implicated in the development of the disease.

“It’s going to take a concerted and global effort to develop life-changing treatments, but this seminal study also gives us hope that research will win, and it gives us the opportunity to work on new treatment targets.

“Well-conducted collaborative efforts like this, including researchers at the UK Dementia Research Institute, underline the positive impact that investment in dementia research in the UK can deliver. Alzheimer’s Research UK are proud to have co-founded the UK DRI and must thank the dedication of our supporters across the UK for making this work possible.”

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