Dementia affects 850,000 people in the UK and, while Alzheimer’s is the most common cause of the condition, a number of different diseases can lead to the development of symptoms. Dementia with Lewy Bodies (DLB) is the third leading cause of dementia in the UK and around 100,000 people in this country are living with the disease.
DLB involves a build-up of a protein called alpha-synuclein inside nerve cells, where it can form toxic clumps called Lewy bodies. These toxic clumps damage nerve cells. While this process is at the centre of our understanding of DLB, Dr Daniel Erskine has identified a different brain change that could have an important effect on how the disease develops and causes symptoms.
This key change occurs in ‘interneurons’, despite the fact these toxic clumps don’t form inside them. Interneurons are nerve cells that coordinate the activity of groups of brain cells that are necessary for functions like learning and memory. In this project, the team will explore how DLB damages interneurons.
Understanding how the disease causes damage to the brain is vital in finding new drug targets to help discover a life-changing treatment.
Increased amounts of a protein called alpha-synuclein is a key hallmark of dementia with Lewy bodies (DLB). In this project, Dr Erskine will investigate how alpha-synuclein affects interneurons compared to other brain cells. To do this, he will employ a Nobel prize-winning technique that uses stem cells to form different types of brain cells. Then, he will add alpha-synuclein to see how the cells respond, and if they respond differently.
By examining this brain tissue, Dr Erskine can study if damage to interneurons is linked to memory and thinking problems. The team will count how many interneurons are present in brain tissue of people with DLB compared to tissue unaffected by DLB. This will show whether the brain tissue from people with DLB has a reduced number of interneurons. Dr Erskine can then link the number of interneurons to scores on memory and thinking tests, revealing if changes in the number of interneurons contribute to DLB symptoms.