Understanding the role of mitochondria in dementia with Lewy bodies

Research project: Analysing somatic mitochondrial DNA alterations in single brainstem neurons of Lewy Body Dementia patients to understand cell-type variation and related plasticity

Lead Investigator: Dr Ilse Pienaar

  • Institution: University of Sussex
  • Grant type: PhD Studentship
  • Duration: 3 years
  • Amount: £85,000

Why did we fund this research?

Comments from our Research Network volunteers:

 ‘I think that research into the lesser known and less researched types of dementia such as dementia with Lewy bodies is very important.’

Project summary

Dementia with Lewy bodies is a disease that may cause 10-15 percent of all cases of dementia. We understand much less about dementia with Lewy bodies than the more common causes of dementia such as Alzheimer’s disease, as the research is limited.

This project will improve our understanding of why certain types of nerve cell are damaged in dementia with Lewy bodies and may inform future treatments to prevent this damage.

The background

Dementia with Lewy bodies is characterised by tiny deposits of a protein called alpha-synuclein that appear in nerve cells in the brain. These deposits are called Lewy bodies and are linked to low levels of important chemicals that carry messages between nerve cells as well as a loss of connections between nerve cells.

The symptoms have similarities to Alzheimer’s disease and to Parkinson’s disease, including problems with alertness and awareness, hallucinations and delusions, and movement problems such as slow, stiff movement and a shuffling walk.

Dementia with Lewy bodies doesn’t affect all nerve cells equally. Previous research suggests that nerve cells that use a particular chemical messenger to send signals (called acetylcholine) are particularly vulnerable, whilst nerve cells that communicate using another chemical messenger (called GABA) are relatively unaffected.

Comparing the changes in these different types of nerve cell could provide important information about how the disease causes loss of brain cells, and help develop future treatments.

What does this project involve?

The researchers are particularly interested in understanding changes in mitochondria. Mitochondria are the powerhouse of the cell, and they contain DNA which allows them to produce this energy.

Interestingly, this DNA is not only determined by what we inherit form our parents, it can also acquire damage over the course of our life. When the DNA is damaged, this can reduce energy production and even trigger the death of the nerve cell.

The researchers want to understand if damage to the DNA in the mitochondria explains why some types of nerve cells die, but others are less affected. The PhD student will investigate changes in nerve cells from a particular part of the brain that is affected by dementia with Lewy bodies (the pedunculopontine nucleus). 

They will carefully extract nerve cells from brain tissue that has been donated by people who had dementia with Lewy bodies. They will use special techniques to extract the DNA from these cells and look for changes. The researchers will compare the number of errors in the DNA code between different nerve cell types (those that use acetylcholine and those that use GABA). They will also compare the changes in brain tissue from people who had dementia with Lewy bodies to changes in brain tissue from healthy people.

How will this project help people with dementia?

Dementia with Lewy bodies is an important but relatively little understood cause of dementia. There are some medications that may help with the symptoms but there are no treatments that can stop the disease from getting worse over time.

This project will improve our understanding of the causes of nerve cell loss in dementia with Lewy bodies. This could provide important insights that contribute to the development of future treatments for the disease.