Understanding how Alzheimer’s disease affects specific brain cell networks

Research project: Disentangling network dysfunction in Alzheimer's disease pathology: cause, consequence and rescue
 

Lead Investigator: Dr Iris Oren

  • Institution: University of Edinburgh
  • Grant type: Project 
  • Grant amount: £224, 773
  • Start date: October 2013
  • Completion date: September 2016

What was the project, and what did the researchers do?

Alzheimer's disease is a physical disease that affects the brain. During the course of the disease, proteins build up in the brain to form structures called 'plaques' and 'tangles'. This leads to the loss of connections between nerve cells, the cells in the brain that send information, and eventually to the death of nerve cells themselves. The first part of the brain to encounter these plaques is usually the hippocampus, which is important in short term memory. 

The hippocampus contains two main types of brain cells: excitatory cells that send electrical signals to switch on other cells and create a physical response in the body like storing a memory, and inhibitory cells that stop signals from being sent.  These inhibitory cells are very important in the hippocampus, and stop this part of the brain from being constantly switched on which can result in seizures, such as in epilepsy. 

The aim of this project is to understand how the control of these inhibitory cells is affected in Alzheimer’s disease. The researchers used mice that have been genetically changed to develop the protein plaques in the brain. They looked at the strength and frequency of the electrical signals in the brain of the mice using a method called Electroencephalogram (EEG) recording. EEG has previously shown that the inhibitory network is damaged in people likely to develop dementia. This method will also be used to determine if any seizures are occurring in these mice. 

As well as the activity of the brain the researchers looked to measure the number of connections made by the inhibitory cells in both the mouse brain and in human brains from people with Alzheimer’s disease. 

What were the key results, and how will this help in the fight against dementia?

The researchers found that there was a change in the inhibitory cell network in the brains of the Alzheimer’s disease mouse models. Interestingly, this was in an area of the brain that has been shown to be affected early in Alzheimer’s disease, and is altered in brains of people with epilepsy.

Using the EEG they found that the mice with damaged inhibitory networks were more prone to seizures, especially during sleep. This finding ties in with the symptoms seen in epilepsy, and may provide some information on the behavioural changes seen in people with Alzheimer’s disease during the night time.

Taken together these results provide initial evidence for an interesting therapeutic target for early stage Alzheimer’s disease. If we could reduce damage to the inhibitory network in the brains of people with Alzheimer’s disease, or switch these inhibitory signals back on we may be able to reduce the behavioural symptoms of Alzheimer’s disease in the early stages.  

What happened next? Future work and additional grants

The researchers in this project have got a lot of initial information regarding the problem of the loss of the inhibitory network in the brain of Alzheimer’s disease mouse models. They are keen to continue their work in this area, looking more specifically at different areas of the brain, as well as at the network in human brains.

Dr Oren has been awarded two pilot project grants from Rosetrees Trust and Alzheimer’s Research UK to continue this work.

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