Exeter part of largest genetic study on Alzheimer’s identifying new DNA risks
A large-scale international study offers new insights for understanding Alzheimer’s disease and developing future treatments.
The University of Exeter led PROTECT study was part of the research, led by Vrije Universiteit Amsterdam and published in Nature, which sheds clearer light on the role of immune cells within the brain, as well as several specific neuronal cell types.
The scientists identified 127 regions in human DNA associated with the risk of developing Alzheimer’s disease – 48 of which had not previously been mapped in this context. These findings provide researchers with a deeper understanding of the biological processes that contribute to the onset of the disease and may aid in the development of new therapies.
Professor Anne Corbett of the University of Exeter is PROTECT study lead and said: “This exciting new genetic analysis has uncovered new information on how our genes influence our risk of Alzheimer’s disease. We’re delighted that the PROTECT-UK study contributed to these important new findings. PROTECT collects genetic samples from all participants through a simple at-home saliva sample. This data can then be combined with cohorts from around the world to help us to better understand dementia risk and how it can be treated.”
Alzheimer’s disease is the leading cause of dementia. The number of people living with dementia is expected to rise sharply worldwide, with projections suggesting more than 150 million cases by 2050. Although genetic factors play a significant role in the risk of developing Alzheimer’s, it is not yet fully understood which specific genes and biological processes cause or influence the disease.
This is the largest genetic association study on Alzheimer’s to date, bringing together data from individuals with diverse genetic backgrounds. Researchers analyzed genetic data from approximately 2.8 million individuals, including 183,620 people with Alzheimer’s.
A significant finding is that the results further underscore the role of microglia – immune cells in the brain involved in tasks such as clearing away harmful substances and damaged cellular material.
Research lead Danielle Posthuma of Vrije Universiteit Amsterdam said: “We already knew that immune processes play an important role in Alzheimer’s disease. What makes this study particularly valuable is that we can now connect new genetic risk factors to more specific biological processes, while also uncovering evidence pointing to the involvement of other brain cell types. This gives us a more detailed picture of the biology underlying Alzheimer’s and provides new directions for investigating potential treatments,”
Importantly, the study also reveals new insights beyond the immune system. For the first time, the researchers identified several specific types of neurons that are enriched for genetic signal and may play a key role in the development of Alzheimer’s disease. This opens up new directions for investigating how the disease develops.
These genetic associations serve as a starting point rather than proof that targeting a specific gene will necessarily result in an effective treatment. Follow-up research is required to determine which of these identified associations play a causal role, and whether intervening in these processes is both safe and meaningful.
The scale of this study demonstrates the value of collaboration between academic researchers, biobanks, and industry. By pooling data from 30 research groups, the investigators were able to detect genetic associations that might have gone unnoticed in smaller-scale studies. The study was conducted under the umbrella of the international Psychiatric Genomics Consortium, whose Alzheimer’s disease working group is co-led by Danielle Posthuma and Ole Andreassen of the University of Oslo.
