Studying loss of connections between brain cells

Read about a research project we funded into investigating axonal injury responses in tau-mediated neuronal degeneration.

Lead applicant: Dr Katrin Deinhardt

Institution: University of Southampton

Grant type: PhD

Amount awarded: £84,953

Duration: 3 years

Why did we fund this project?

Comments from members of our Research Network:

'The student is being trained in the use of modern technologies and techniques in an excellent environment with the distinct possibility of creating a foundation for new therapeutic approaches.'

'The academic environment looks as if it will provide the student with excellent support and access to cutting edge technology and methodology.'

'A well-presented and argued PhD student work plan with a potential outcome which could contribute to the treatment of Alzheimer's disease and a better understanding of it.'

What do we already know?

Alzheimer's disease is caused by the toxic build-up of the proteins tau and amyloid in the brain, which causes neuron cells to die. Studies have shown that connections between neuron cells, known as synapses, are disrupted long before the cells begin to die. Breaking these connections causes neurons to be lost from the network of signalling in the brain and trigger the symptoms of dementia. This generated the idea that Alzheimer's is a disease of synapses. 

Early responses in neurons caused by protein accumulation predict whether the neuron will show synapse loss. These responses look like stress responses reported in other cells of the body, suggesting that neurons are injured a long time before synapse loss and the devastating neuronal disintegration and cell death. Surprisingly, little is known about when the first disease causing events happen and how these produce the progressive sequence that leads to nerve cells becoming sick, disconnecting and then dying.

What does the project involve?

The project will identify significant injury-related changes that happen in the brain to decipher if the injury responses, which are seen early during disease, provide therapeutic routes that can be targeted by drugs. This work will provide a platform to develop potential new avenues to Alzheimer's treatments designed to act at early pre-emptive stages of the disease process that is happening in nerve cells.

The researchers will use mice and cells grown in the lab that produce abnormal tau protein. Using this strategy, they hope to identify early injury responses of the nerve cells.

How will this benefit people with dementia?

In dementia, neuronal networks disintegrate and nerve cells die, and we have no way to protect these cells. Designing protective strategies for the intact brain is difficult as we lack insight about the earliest events that drive Alzheimer's disease. This research hopes to establish a foundation for new therapeutic approaches by identifying how early events alter nerve cell function and which potential targets are key to nerve cell protection.

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