Summary

Dr Natalie Connor-Robson and Professor Julie Williams, with support from BRACE-funded PhD student Johanna Maninger, and their team, are researching two important genes in Alzheimer’s disease. They are looking at how these genes work together to lead to the progression of Alzheimer’s to hopefully find potential targets for new treatments.  

What do we already know?

Most cases of Alzheimer’s disease occur in patients 65 years and older and are known as sporadic or late-onset Alzheimer’s disease. Although more common, this later form of Alzheimer’s is much harder to study as there are lots of genes involved. This research aims to address this gap in the field. 

Previous research into the genetics of Alzheimer’s disease has identified two key genes as the most important genetic risk factors. These genes are called APOE and BIN1. They each have different roles in the build-up of amyloid beta (a key component of the development of Alzheimer’s disease). However, not much is known about how these genes come together to alter cell behaviour. 

What is this project trying to find out?

Dr Natalie Connor-Robson and Professor Julie Williams with support from Johanna Maninger and their research team will look to understand the relationship between APOE and BIN1 in late onset Alzheimer’s disease. They will use stem cells to generate key types of cells in the brain called astrocytes and microglia. This research will investigate how the APOE and BIN1 genes affect cells and the processing of amyloid beta in the brain. 

Why is this important?

The results from this project will provide new insights into how two of the most significant Alzheimer’s risk genes affect brain cells. Ultimately, this knowledge may help identify potential targets for future drug treatments, giving hope to those at risk of developing Alzheimer’s and their families. 

What has been achieved so far?

To study the effects of genes called APOE and BIN1, the team has used advanced gene-editing technology called CRISPR to modify these genes in the stem cells known as iPSCs. Once they had these modified cells, they used methods in the lab to turn them into microglia and astrocytes.  

So far, the team has begun running a series of functional tests to understand how microglia behave in the presence of APOE and BIN1 variations.  

By examining these processes, the team aim to uncover how the combination of APOE and BIN1 variations affects microglia’s ability to perform these vital functions. Understanding these changes could shed light on how these genetic factors contribute to the development of Alzheimer’s disease.