Understanding the genetics of depression in Alzheimer’s disease

Research project: Using genetic risk of depression to find new pathways involved in the development of depression in Alzheimer’s disease 

Lead Investigator: Dr Lindsey Sinclair

  • Institution: University of Bristol
  • Grant type: Junior Fellowship
  • Duration: 30 months
  • Amount: £224,825.00

Why did we fund this research?

Comments from our Research Network volunteers:

‘To understand the mechanism of depression in AD is crucially important for patients and carers especially given the fact that currently available antidepressants are not working to ameliorate this condition’.

Project summary

Depression in people with Alzheimer’s disease is common but hard to treat and antidepressants typically don’t work as well. While a family history of depression increases the risk of developing depression in people with Alzheimer’s disease, the reason for this isn’t clear. This study will compare genetic risk of depression in different populations to better understand the underlying biology of and link between depression and dementia.     

The background 

Depression in people with dementia is more common than it is in older adults without dementia, but we still don’t understand the underlying cause of depression that could give us clues as to why this is. 

On top of this, there are no effective treatments for depression in people with dementia as standard antidepressants don’t seem to work.

We don’t know if this is because there is a different disease process or if the brain areas required for the treatments to work have been affected by the dementia. Our lack of understanding about depression have made answering these questions challenging. 

What does this project involve?

In this project the researcher wants to gain a better understanding of depression in dementia.

Firstly, she will look at brain scanning images of the brain to identify areas which are most affected in depression during Alzheimer’s disease. 

The next step will be to assess genetic risk of depression and establish whether people with a genetic predisposition to depression are more likely to also develop depression during Alzheimer’s disease. 

Lastly Dr Sinclair will study post-mortem brain tissue from people who had depression comparing individuals at high and low genetic risk of depression. This will help us to better understand the genes and pathways that are activated and how these changes cause depression. 

How will this project help people with dementia?

This project will help us to better understand the differences between depression in people with and without dementia and identify the biological processes causing it. Understanding these processes can help create treatment options for people with dementia that will have a real impact on their lives.