More than 40 genes have been linked for the first time to Alzheimer’s disease in a “landmark” study, paving the way for better diagnosis and treatment.
Global scientists, including from the UK, carried out the biggest research project of its kind looking at the genome (genetic material) of more than 100,000 people with Alzheimer’s.
Their findings suggest the disease is caused by a multitude of different factors and provide new evidence for the role of a specific protein involved in inflammation.
The team hopes that, in future, they will be able to determine which factors put people at risk of Alzheimer’s and to develop therapies that better treat the condition.
Another possibility is that genetic testing will identify those people most at risk of developing Alzheimer’s before their symptoms appear.
This piece of work is a major leap forward in our mission to understand Alzheimer’sProfessor Julie Williams
The study, published in Nature Genetics, identified 75 genes associated with an increased risk of developing Alzheimer’s disease, including 42 genes not previously implicated in the condition.
It also confirmed previous findings regarding the proteins amyloid-beta and tau, which build up in and around nerve cells as Alzheimer’s progresses, and found that inflammation and the immune system play a role in the disease.
A group of 111,326 people with Alzheimer’s disease were compared with 677,663 healthy individuals to look for differences in their genetic make-up.
The findings showed for the first time that a specific biological signalling pathway involving TNF-alpha (a protein with an important role in inflammation and the immune system) is implicated in Alzheimer’s.
The research also offered more evidence that the dysfunction of microglia (immune cells in the brain that are responsible for eliminating toxic substances) contribute to the way the disease progresses.
This study more than doubles the number of identified genes influencing risk for the more common form of Alzheimer’s diseaseDr Rebecca Sims
Ongoing and future studies will now look closer at the genes and how they are implicated in the death of brain cells, which could lead to new treatments.
A genetic risk score has also been created that could determine how likely it is that patients with cognitive impairment will develop Alzheimer’s disease within three years of symptoms appearing.
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 results support our growing knowledge that Alzheimer’s disease is an extremely complex condition, with multiple triggers, biological pathways and cell types involved in its development.
“Components of our immune system have a big role to play in the development of the disease.
“For example, immune cells in the brain known as microglia are responsible for clearing out damaged tissue, but in some people that may be less efficient which could accelerate 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 winDr Susan Kohlhaas
“Lifestyle factors such as smoking, exercise and diet influence our development of Alzheimer’s, and acting to address these now is a positive way of reducing risk ourselves.
“However, 60-80% of disease risk is based on our genetics and therefore we must continue to seek out the biological causes and develop much-needed treatments for the millions of people affected worldwide.”
Dr Rebecca Sims, senior research fellow at Cardiff University and UK Dementia Research Institute co-investigator, and co-leader of the research, 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.”
Dr Susan Kohlhaas, director of research at Alzheimer’s Research UK, said: “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.”
Professor Bart De Strooper, director of the UK Dementia Research Institute, said: “Ambitious studies like this are the fuel for the breakthroughs we need in dementia research.”
Eight countries, including the UK, US and Australia, took part in the study.
Alzheimer’s disease is the most common cause of dementia and affects more than 850,000 people in the UK.