Understanding effects of damage to an area of the brain susceptible to degeneration in Alzheimer's disease

Read about a research project we funded into the molecular and functional characterisation of the locus coeruleus-noradrenergic nucleus in Alzheimer’s disease.

Lead Investigator: Dr Jerome Swinny 

  • Institution: University of Portsmouth
  • Grant type: PhD studentship
  • Amount: £80,000
  • Start date: October 2013
  • End date: September 2017

The background

The locus coeruleus (LC) is a region of the brain that is susceptible to degeneration in ageing and is particularly vulnerable in dementias. Cells of the LC produce the chemical noradrenaline that is important in controlling behaviours such as thinking, memory and emotion. 

The LC also helps in developing strategies to cope with stressful life events and is essential for our stress response. The loss of LC neurons and the decrease in noradrenaline levels has a devastating effect in dementias, depriving people not only of their ability to consciously make sense of their world but also the emotional stability that this neurochemical ensures. 

Understanding the changes to the LC that result in Alzheimer’s disease is important for developing new treatments to address thinking and memory problems but also emotional distress that can be neglected at the later stages of the condition. 

What did the project involve?

This research firstly aimed to investigate how Alzheimer’s disease affects the function of this vulnerable group of nerve cells that produce noradrenaline in healthy mice and a mouse-model of Alzheimer’s disease. 

The research team studied how these cells react to chronic stress to understand the changes that occur in these cells that lead to neurodegeneration, and how chronic stress may contribute to this process.

What were the key results? 

The research team found in the healthy mouse, cells in the LC produced a number of proteins vital for controlling the amount of noradrenaline released.

For the first time they were able to show that the LC in the mouse model of Alzheimer’s disease showed changes to these proteins and this affected the function of these cells. 

Dr Swinny believes that the cells in the LC in the mouse model of Alzheimer’s disease behaved differently and that this could affect the amount of noradrenaline released. This may help to explain why people with Alzheimer’s disease can experience mood instability and impulsivity.

How will this benefit people with dementia?

This research has helped us to understand more about the very early stages of Alzheimer’s disease and specifically the impact changes to cells that produce noradrenaline may have. 

Dr Swinny and his team have been able to identify potential targets for therapeutic intervention to tackle behavioural and emotional symptoms that people with Alzheimer’s disease experience.

Next steps

Dr Swinny will continue this important area of research and apply for additional funding to support this work. They are collaborating with scientists based at University of Southampton to test drugs which are currently available which target the pathways they have identified during this research project.

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