A new international study has found 42 genes associated with an increased risk of developing Alzheimer's disease that had not been previously known.
Alzheimer's disease is a neurodegenerative disease and the most common form of dementia. A person's genetics plays a large role in their risk of developing the disease; thus, researchers in this novel study were trying to understand the genetics underlying the disease. The collaborative study was conducted across eight different research centres across the world, including the UK where the collaboration was co-led by researchers Dr Rebecca Sims and Professor Julie Williams from the UK Dementia Research Institute at Cardiff University.
Professor Williams 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 study, published in Nature Genetics, was the largest of its kind, analysing 111,326 Alzheimer's disease cases and 677,663 healthy control cases. Using genome-wide association to identify differences in genetic makeup between the Alzheimer's and healthy control cases, the researchers identified a total of 75 genes associated with an increased risk of Alzheimer's, 42 of which had not been previously linked to the disease.
When the researchers investigated what biological pathways the risk genes were associated with, they found pathways involved in amyloid-beta and tau, two proteins which aggregate in the brains of people with Alzheimer's disease, and pathways involved in microglia, the main immune cell type of the brain.
While the important role of amyloid, tau, and microglia in Alzheimer's disease had been previously known, notably 31 of the newly identified risk genes were associated with biological pathways not previously linked with the disease, including a specific signalling pathway of the protein TNF-alpha, which has an important role in the immune system and inflammation.
With their findings, the researchers were also able to create a new genetic risk score to predict how likely a person with cognitive impairment will go on to develop Alzheimer's disease later in life.
In the future, researchers are able to focus on the novel risk genes identified in this study and try to uncover how they contribute to Alzheimer's disease. Professor Bart De Strooper, the director of the UK Dementia Research Institute at University College London, who was not involved in the study, said: 'Ambitious studies like this are the fuel for the breakthroughs we need in dementia research. They show us that there is still much to learn about neurodegeneration, and continued investment in fundamental, discovery science is key to unlocking the secrets of Alzheimer's and other dementias.'