New funding will support research into gene activity in different types of brain cells to find changes associated with Alzheimer’s disease.

A £1.5 million grant from the Medical Research Council (MRC) will, for the first time, support new research examining changes in how genes function in specific brain cell types to better understand the development of Alzheimer’s disease.

The study will be led by a team at the University of Exeter with co-investigators at the UK DRI Centre at Imperial, the University of Essex and the University of Bristol.

Alzheimer’s disease is a chronic neurodegenerative disorder that affects more than 26 million people worldwide, with no treatment available to improve the course of the disease. Despite major advances in identifying genetic risk factors, uncertainty remains about the specific genes that cause the condition and how their function is dysregulated in its progression.

Previous research has shown that Alzheimer’s disease is characterised by changes occurring in certain cell types, for example, the extensive loss of neurons. Therefore, it is critical to measure gene activity in each different brain cell type individually to understand how they are linked to the development of the condition. Mapping the differences will potentially enable a step-change in unravelling the mechanism of Alzheimer’s disease.

Study lead Professor Jonathan Mill, from the University of Exeter, said: “We’re delighted that our project has been funded by the Medical Research Council. By identifying genomic changes in specific cell types in the brain that are associated with Alzheimer’s disease, we will be in a unique position to understand more about the molecular processes involved in this terrible condition and identify pathways that can be hopefully targeted by novel drugs and treatments.”

The extensive data to be collected in the study and the methods used will be made freely accessible, to provide an Open Science resource to the wider research community and stimulate dementia research across the world. 

Co-Investigator Dr Sarah Marzi, Edmond and Lily Safra Research Fellow and UK DRI Fellow at Imperial, explains: “Our team at the UK DRI Centre at Imperial will be generating chromatin profiles in brain cells of people affected by Alzheimer's disease and controls. We will look at the histone modification H3K27ac, which marks active regulatory elements. This will allow us to identify genomic regions that are up- or downregulated in disease across multiple affected cell types.

“In total, we will generate 600 genome-wide histone acetylation profiles using a novel technique called CUT&Tag. These will then be integrated with further epigenetic and gene expression profiles generated by the team in Exeter to deeply characterize and understand cell type-specific regulatory variation in Alzheimer's disease.”

Commenting on the broader significance of the trial, Dr Marzi added: “I am absolutely delighted to be part of this brilliant team and exciting project to comprehensively profile gene regulation in Alzheimer's disease. I am optimistic that by systematically studying regulatory variation in disease-relevant cell types, we can pinpoint early disease mechanisms to specific cell types and untangle downstream consequences, giving us the best shot at identifying targeted prevention strategies and treatments.”

This article was adapted from a press release by the University of Exeter

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