Posted on 5 April 2022
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Alzheimer’s disease is the most common form of dementia, and it is estimated that 60% to 80% of one’s risk of developing the disease is genetic. Identifying genes that play a role in Alzheimer’s can give us clues as to what’s happening in the brain of diseased patients, which may in turn help us to develop treatments.
What did the researchers do: In this study, researchers analysed genome-wide association studies, a type of study in which scientists look for genetic factors associated with a specific outcome within a large population sample. In total, the study included the genomes of around 100,000 people with Alzheimer’s and 600,000 healthy people, making it the largest genetic study of Alzheimer’s disease to date.
Key takeaway(s) from this research: Researchers identified 75 genes that were associated with an increased probability of having Alzheimer’s disease, including 42 genes that had not previously been implicated. As might be expected, some of these genes were related to the processing of amyloid precursor protein, the precursor of the amyloid beta protein that forms amyloid plaque within the brains of Alzheimer’s patients. However, the identified genes also point to another key player in Alzheimer’s disease: the dysregulation of the brains resident immune cells, known as microglia, and the activation of molecular pathways that promote inflammation in the brain.
If [at the outset] we’d seen the genetics of common disease, we would’ve said this is an immune disease.Study co-author Prof Julie Williams, director of the UK Dementia Research Institute at Cardiff University
Scientists have long thought that a malfunctioning immune system leading to inflammation (a process meant to help the immune system fight pathogens) could be driving Alzheimer’s disease, and the genetic findings here support that idea. Highlighted gene variants include those that cause microglia to work too aggressively when cleaning up damaged tissue, leading to more damage instead. Others involved lowering the threshold for the ‘eat me’ signals produced by neurons when they are damaged, causing otherwise healthy neurons to be destroyed. Many genes affecting signalling by inflammatory molecules in general were also implicated.
This study expands our understanding of the genetic underpinnings of Alzheimer’s, sets the stage for further research and hopefully new treatments. The data has also allowed scientists to create a genetic risk score that could predict which patients would develop Alzheimer’s within the first three years after developing cognitive impairment. This score is not yet ready for clinical use, but could be used for recruitment in clinical trials in which drugs must be administered at the earliest stages of disease.
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