Understanding why certain parts of the brain are vulnerable to Alzheimer’s disease

Read about a research project we funded about understanding the basis for selective vulnerability of different neuronal populations to tau toxicity.

Lead Investigator: Dr Lovesha Sivanantharajah
Institution: Bangor University
Grant type: Junior Fellowship
Duration: 36 months
Amount: £224,447

Why did we fund this project?

Comments from members of our Research Network:

'This is a novel approach to the study of tau in dementia and one which I think could in time be turned to great advantage in the treatment of dementia.'

'As tau seems to be a common factor in nearly all of the research, I think that the more information we can obtain about it, the sooner we will understand it's part in the onset of dementia.'

'This project has the potential to extend our understanding of AD and benefit the lives of people affected by dementia. The principal applicant's qualifications and experience are impressive; providing a solid base for the success of the proposed research.'

What do we already know?

Alzheimer's disease is associated with the abnormal accumulation of two proteins in the brain. One of these proteins is called the amyloid protein and builds up into harmful clumps called plaques which are found just outsidebrain cells. The other protein, tau, forms toxic clumps known as tangles that are mostly found inside brain cells. There are also a number of other less common types of dementia, for example frontotemporal dementia, which are associated with accumulation of the tau protein.

In the early stages of Alzheimer's disease, the tau tangles only form in particular brain cells in certain parts of the brain. It particularly affects the areas associated with learning and memory, which is why problems with this are associated with symptoms of the condition. In later stages of the disease, other areas of the brain become affected, but some brain regions do not appear to be as affected.. Dr Sivanantharajah wants to better understand why certain areas are prone to the formation of tau tangles while others seem to be protected.

What does this project involve?

One reason that certain brain areas are disproportionately affected could be differences in the types of cells that are found in those regions. Research so far hasn't looked in detail at how tau tangles affect different types of cells. In this project, Dr Sivanantharajah will use cutting edge techniques in genetics research to identify the types of brain cells that are vulnerable to the formation of tau tangles and those that are more resistant. 

The researchers will carry out the experiments using fruit flies to look at the effects of different versions of tau. The new genetic tools they have developed will allow them to examine how these forms of tau affect 30 different brain cell types in the nervous system of the fly. 

Firstly, they will look broader effects such as how the shape and structure of the cells are affected. Then they will look in greater detail to see where tau tangles are found in the cells, and whether they cause damage to the part of the cell that contains our DNA. They will also investigate the effect of tau on the mitochondria, which is the part of the cell that is important for producing energy .

How will this benefit people with dementia?

So far it is unclear why some parts of the brain are affected by the causes of Alzheimer's disease and others are not. This study will advance our understanding of why different types of brain cell and different parts of the brain are affected by diseases such as Alzheimer's. One long-term goal of the project is to find the genetic aspects that underlie the difference between a cell that is vulnerable to abnormal tau, and a cell that is protected. Identifying these genetic factors could provide new avenues to be explored for potential future treatments.