Dementia Research Leaders: Annabelle Chambers

Introducing Annabelle Chambers, Postdoctoral Researcher. She is part of our Dementia Research Leaders programme that supports people from biomedical, clinical and social science backgrounds.

What is your research background?

I first knew that I wanted to do research in neuroscience when I was a 19 year- old undergraduate at the University of Leeds; I had just enrolled on a course on 'Central Nervous System disorders' as part of my Pharmacology degree. From the very first lecture, I was adamant that this was the career path I wanted to follow.

There is still so much to discover within the brain, with regards to how cells work, how they interact with one another and what can go wrong, and I wanted to be someone that sought to find answers to these numerous questions.

Postdoctoral researcher Annabelle Chambers

I went on to complete a PhD at the University of Nottingham, looking at how chemotherapy treatment affects cognitive function in the brain, and possible ways this could be prevented. There were a lot of similarities to neurodegenerative disorders such as dementia so I decided to continue in this field. In 2015, I began my postdoctoral work as a Dementia Research Leader in the lab of Dr Stephen Wharton at the University of Sheffield, funded by Alzheimer's Society.

I am looking at the links between type 2 diabetes, metabolic syndrome and dementia.

Metabolic syndrome, diabetes and dementia

Metabolic syndrome is when someone experiences risk factors for diabetes but does not have the full condition. Both metabolic syndrome and type 2 diabetes are characterised by deficiency in how the body processes nutrients such as sugars, along with resistance to the hormone that regulates our blood sugar levels, insulin. While this is already associated with vascular dementia, there is now evidence that these disorders could contribute to the development of Alzheimer's disease, although the mechanisms behind this are unclear.

During my project, the main question I am asking is 'what is the contribution of diabetes to cognitive impairment?' This will go hand-in-hand with looking at possibilities as to why this occurs. There are numerous theories, which include that diabetes affects vascular mechanisms (those that involve blood vessels), or through other possible direct effects on brain cells which may cause early ageing. One aspect of my project is investigating the interaction of glucose with proteins in the brain that are associated with Alzheimer's disease, including the hallmark amyloid and tau proteins.

I am also looking at the effects of antioxidants in the brain and how these associate with diabetes and Alzheimer's disease. Other possibilities could include damage to the brain by an overactive immune system, whereby substances associated with inflammation can damage cells and stop them performing normal activity in the brain.

One part of this involves finding out how dementia can affect proteins such as IRS1 or sirtuins that are associated with diabetes. For example, we are hoping to understand whether dementia causes these proteins to behave differently. My studies so far suggest that expression of one protein associated with diabetes matches the severity of Alzheimer's disease, so I will look at other markers to see if I see similar results. As proteins are related to specific pathways in cells, this will allow me to determine which ones may have a more prominent role in cognitive function.

Diabetes, dementia and genetics 

Over the next few years, an exciting part of my project will look at how diabetes and dementia affect the body at the genetic level. I will isolate specific cell types from brain tissue - neurons, astrocytes and blood vessels - and analyse these at a molecular level in molecular detail using a special microchip that allows us to examine thousands of different genes in a short space of time. This will highlight which of the genes are switched on and off in different disease states, to determine how genes are affected in mild cognitive impairment when compared to advanced Alzheimer's disease. It will hopefully highlight new targets for the development of future treatments. 

I have the privilege of working with donated brain tissue from the MRC Cognitive Function and Aging study, which is one of the only studies in the UK that is an unbiased, multi-centre, population-based study. This means my work covers the whole spectrum of cognitive function in brains from people over the age of 65. This allows me to measure specifically how genes and proteins expression changes through aging and more specifically, the progression of Alzheimer's disease.

The UK has an increasingly ageing population, and if we combine this with a growing number of type 2 diabetes diagnoses, it is clear that we need to further our knowledge into the relationships between these two disorders, and I am proud to be a part of this research.

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