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

Lead Investigator: Dr Jerome Swinny 
Institution: University of Portsmouth
Grant type: PhD studentship
Duration: 3 years
Amount: £80,000
Scientific Title: Molecular and functional characterisation of the locus coeruleus-noradrenergic nucleus in Alzheimer’s disease

Why did we fund this project? Comments from members of our Research Network:

'[I] must encourage this very fundamental work bearing as it does upon not only cognition but also emotional behaviours.'

'Another important step to identifying what causes behaviour changes and loss of abilities in people with dementia.'

'I enthusiastically support this project which puts the emotional aspects of Alzheimer’s disease and the stress and anxiety suffered by both people with dementia and their carers at the heart of this scientific research.'

What do we already know?

A region of the brain that is susceptible to degeneration in ageing and is particularly vulnerable in dementias is the locus coeruleus (LC). Cells of the LC produce the neurochemical noradrenaline, which acts throughout the brain to control fundamental human behaviours such as cognition and emotion.

In addition, the LC helps in developing strategies to contend with stressful life events and is thus essential for one's stress response.

Thus, the loss of LC neurons and consequent 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.

Therefore, understanding the changes to the LC that result in Alzheimer’s disease-induced LC dysfunction is central to the design of therapies that address not only the cognitive impairments associated with Alzheimer’s disease but also the emotional disturbances that co-exist, but are often neglected in terms of palliative care.

What does this project involve?

This research will firstly investigate how Alzheimer’s disease alters the function of this vulnerable group of noradrenergic neurons in normal mice and an Alzheimer’s disease mouse-model.

A combination of electrophysiology, measuring the activation patterns of certain neurones, and understanding how these cells react to chronic stress will help the researchers to understand the changes that occur in these cells to lead to neurodegeneration, and how chronic stress may contribute to this process in a model that is already prone to the development of Alzheimer’s disease pathology.

Finally, the researchers will compare the efficacy of currently used antidepressants in their ability to reverse the stress-induced depressive behaviour of Alzheimer’s disease model mice.

How will this benefit people with dementia?

This research will help us to better understand the very early stages of Alzheimer’s disease pathology, uncovering potential targets for therapeutic intervention. The study will also provide scientific evidence for the effectiveness of antidepressants in treating the co-existing behavioural and emotional symptoms that people with Alzheimer’s disease experience.