Finding ways to boost resilience to Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia. It is characterised by toxic proteins, amyloid and tau, that form clumps in the brain.

Although everyone with Alzheimer’s disease has these protein clumps in their brain, not everyone who has these clumps experiences the symptoms of dementia. Scientists call this group of people cognitively resilient.

Discovering why these people are resilient and designing treatments to increase resilience in those at risk will improve the lives of people living with dementia.

Proteins underly all the complex processes happening in our brain. The interaction of proteins allows nerve cells to communicate, form memories, and when things go wrong, to die.

Dr Becky Carlyle from the University of Oxford will measure thousands of proteins in the brain and discover where in nerve cells they are active. This will allow Dr Carlyle to see if there are groups of proteins that act together to make a person cognitively resilient.

This study will discover hundreds of proteins that are different in three groups of people:

• People with Alzheimer’s brain changes and memory and thinking problems (non-resilient).
• People with Alzheimer’s brain changes but with no memory and thinking problems (resilient)
• People with no Alzheimer’s brain changes and no memory and thinking problems (healthy, comparison group)

To follow on from the study, Dr Carlyle will test which proteins are the most important for resilience, in experiments using human nerve cells developed from stem cells.

She will change the levels of resilience proteins in these nerve cells, and see how healthy the nerve cells are, and whether they can still function properly.

The overall aim of the project is to develop an approach that allows large-scale assessments of the protein interactions and their intersection with genetic and environmental risk factors.

This project will identify the proteins that are most important for protecting nerve cells from damage by amyloid and tau. The findings will help reveal potential targets for drugs that could help boost a person’s resilience to Alzheimer’s disease.