Scientists identify 42 new risk genes associated with Alzheimer’s disease in ‘landmark’ study

‘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’

Alzheimer’s is the most common form of dementia, which affects more than 26 million people worldwide (AFP via Getty Images)

Scientists have identified 42 new risk genes associated with Alzheimer’s disease in what is the largest study of its kind.

The findings shed new light on the biological mechanisms at play in Alzheimer’s and raise the prospect of developing treatments for a disease that currently has no cure.

The study, published in the scientific journal Nature Genetics, identified 75 regions of the genome that are linked to Alzheimer’s, including 42 genes never before implicated in the disease.

As well as confirming previous findings relating to the build-up of proteins in brain cells, the research also provides evidence supporting the role of inflammation and the immune system in the condition.

“This study more than doubles the number of identified genes influencing risk for the more common form of Alzheimer’s disease,” said Dr Rebecca Sims, senior research fellow at Cardiff University co-leader of the study.

“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.”

Alzheimer’s is the most common form of dementia, a chronic neurodegenerative disorder that affects more than 26 million people worldwide, with no treatment available to improve the course of the disease.

The condition, which usually develops after the age of 65, has a strong genetic component and most cases are thought to be caused by the interaction of different genetic predisposition factors with environmental factors, such as lifestyle and diet.

As part of an international collaboration, scientists from eight partner countries, including the UK, US and Australia, analysed the genome of more than 100,000 people with Alzheimer’s disease and compared them with over 600,000 healthy individuals to look for differences in their genetic makeup.

Through this approach, the scientists identified 75 genes linked to the condition and confirmed how toxic clumps of protein, called tau and amyloid-beta, slowly accumulate in multiple areas of the brain to help progress Alzheimer’s.

Forming over a number of years, these clusters – known as aggregates – cause cells to die and the brain to shrink, resulting in memory loss, personality changes and difficulty carrying out daily functions.

Some of the 75 genome regions identified by the scientists are implicated in the production and functioning of tau and amyloid-beta.

The research also revealed that disturbance to the action of microglia cells, which are present in the central nervous system and act like a “trash collector” to eliminate damaging substances, plays a role in the progression of Alzheimer’s.

Based on their findings, the researchers devised a genetic risk score to try to better evaluate which patients with cognitive impairment will, within three years of the initial emergence of memory problems, go on to develop Alzheimer’s disease.

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.

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

“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 international collaboration was spearheaded by Professor Jean-Charles Lambert, Research Director of Inserm, the French National Institute of Health and Medical Research.

In the UK, the project was co-led by researchers from the UK Dementia Research Institute at Cardiff University, and funded by the Medical Research Council.

Commenting on the study, Alzheimer’s Research UK said “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.”

Dr Susan Kohlhaas, director of research at the charity, said the study also demonstrates “just how complex Alzheimer’s is, with several different mechanisms implicated in the development of the disease”.

Dementia affects more than 850,000 people in Britain. Some projections suggest the total cost of dementia care in the UK could increase by around 172 per cent, from £34.7 billion in 2019 to £94.1 billion in 2040.