On 4 April, a large group of international scientists published findings on the largest genetic study of Alzheimer’s disease (AD) to date in the journal Nature Genetics. In this project carried out in research centres in eight partner countries including the UK, US, Australia and across Europe, researchers analysed the genome of over 100.000 people with AD and 600.000 cognitively healthy people. In total, the new international study identified 75 genes that were associated with an increased risk of developing AD, 33 of which were already known such as genes implicating hallmark proteins called amyloid and tau. An additional 42 genes that had not previously been linked to the condition have been found. A number of the newly discovered genes are linked to pathways for disease development, immune system and inflammation. The new findings provide compelling evidence to support a role for inflammation and the immune system in the disease.
The findings show 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 AD. Additionally, findings confirmed the involvement of innate immunity and microglial activation in AD. Researchers found that a handful of the new genes may cause the dysfunction of microglia, immune cells in the brain that are responsible for eliminating toxic substances. “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“, said Dr Rebecca Sims, Senior Research Fellow at Cardiff University and UK Dementia Research Institute Co-investigator and co-leader of the study. https://www.nature.com/articles/s41588-022-01024-z
