Understanding the role of supporting brain cells in Alzheimer’s and ageing

Oligodendrocytes are a type of supporting cell in the brain that produce myelin, an insulating layer that forms around neurons. Myelin is important for transmitting electrical signals between cells in the brain. Scientists have shown that disruption to oligodendrocytes and their associated pathways is linked to Alzheimer’s and ageing, but the mechanisms by which the cells influence neurodegeneration remain poorly understood.

In this project, Dr Sarah Marzi, Dr Dervis Salih, Dr Alexi Nott and Dr Rikesh Rajani will look at gene regulation and gene expression in oligodendrocytes, to investigate the mechanisms by which these cells influence neurodegeneration.

In stage I of their project, Dr Marzi and colleagues found that, compared with other brain cell types, oligodendrocytes had the largest number of epigenetic changes in Alzheimer’s. In particular, the way their communication with neurons and microglia – the brain’s resident immune cells – changes in ageing and disease. The scientists were able to link these changes to different pathways and networks, highlighting a role for oligodendrocytes in modulating neuronal and microglial function in disease. 

Building on their initial findings, in stage II the team will dissect the mechanisms by which oligodendrocytes communicate with microglia and neurons, uncovering what makes the brain vulnerable and resilient to ageing related changes. 

The researchers hope their work will identify gene networks in oligodendrocytes that are impacted by age, disease, and contribute to cognitive resilience – and that the findings could lead to new drug targets for Alzheimer’s.