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Taking a Different Approach to Parkinson’s Research

Brain Structure and Function
Taking A Different Approach To Parkinson’s Research
PROFESSOR CAROLINE RAE

Professor Caroline Rae is working on an early detection program for Parkinson’s disease. The program aims to identify those who are at higher risk of developing Parkinson’s disease so treatment can be introduced well in advance. An interview with Professor Rae expands on her work that is leading a new approach to Parkinson’s research.

Why are you taking a different approach to Parkinson’s research?
The main reason is because by the time a person is diagnosed with Parkinson’s they have unfortunately lost areas of their brain which they need in order to recover. We did an initial study looking at a particular area of the brain affected by Parkinson’s disease called the substantia nigra and found that at the point they were diagnosed this part of the brain was not there anymore, it had deteriorated or died.

This is a critical area of the brain that produces a neurotransmitter called dopamine and is involved in motor control. It is eroded by this disease, and by the time a neurologist makes the diagnosis, it is too late to save this important functional part of the brain. This is why it is critical to take a different approach to identify those at risk of the disease well in advance of its symptoms.

What is the substantia nigra and why is it important?
The substantia nigra forms part of the “nigrostriatal circuitry” which connects the substantia nigra with other parts of the brain associated with control of movement and which includes nerves using dopamine as their major chemical communicator or neurotransmitter. Parkinson’s disease targets these nerves in particular, so as they die off brain’s ability to control movement is reduced, producing the symptoms which are a hallmark of the disease.

How does Magnetic Resonance Imaging (MRI) provide new insights?
We use MRI technology to study brain structure and as MRI is evolving it is enabling us to measure brain structure on a much finer detailed level and in more difficult and deeper parts of the brain. The substantia nigra is right down at the bottom of the brain, and it is an area that has not been easy to image. It is also technically challenging to track the connections from the substantia nigra to other parts of the brain. We are one of the few groups in the world here at NeuRA who are looking at substantia nigra connections in those at higher risk of developing Parkinson’s.

We are using a technique called High Angular Resolution Diffusion Imaging (HARDI) to actually look at the wiring between the substantia nigra and other parts of the brain that control movement. We have found that by the time people are diagnosed with Parkinson’s disease they have largely already lost most, if not all, of the connections from the substantia nigra to the rest of the brain.

Why is it important to catch Parkinson’s disease 10-15 years in advance?
We are studying a group of people whose substantia nigra has a feature that makes it give a larger than usual signal in response to pulse of ultrasound delivered by placing an ultrasound probe over a particular place on the skull.

It has been shown by a group in Germany that people with this feature are seventeen times more likely to go on to develop Parkinson’s. In our initial MRI study of these people we have found that they have already
lost up to 60% of the connections between the substantia nigra and the rest of the brain. A neurologist, doing normal clinical checks, will rate these people as healthy. However, if we put very sensitive accelerometers on the fingers of these people while they are doing small tasks with their hands, like lifting an object, we can find subtle signs of motor impairment.

So at this early stage there is still something remaining we can work with.
Early detection means that they can start treatment much earlier when there is still a good part of the substantia nigra and its connections left to remediate.

Our goal is to identify people at risk or at the very early stages
of Parkinson’s, with the aim of identifying these people before they pass the tipping point beyond which it is difficult if not impossible to remediate areas of the brain involved in motor control such as the substantia nigra.

In summary, our work is aimed at finding biomarkers for early detection of Parkinson’s disease to robustly and reliably identify those people most at risk of developing this disease.

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