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Use of Neuronal Exosomes to Predict Parkinson’s Disease

Study Rationale:
In Parkinson’s disease (PD), the build-up of alpha-synuclein inside nerve cells leads to formation of abnormal clumps and death of dopamine-producing cells and other neurons. By the time people develop PD, most of these vulnerable nerve cells have already died and alpha-synuclein clumps form in many brain regions. Nerve cells have different ways of removing toxic proteins: they can destroy them inside the cell or discard them out of the cell in vesicles called exosomes. A tiny fraction of these ejected exosomes enter the circulation and can be detected in blood samples. By studying a group of individuals at high risk of developing Parkinson’s disease, we discovered that nerve cells secrete alpha-synuclein in exosomes years before the disease onset.

Measurement of alpha-synuclein in exosomes can be used to identify people at risk of developing PD or to monitor the effectiveness of disease-modifying therapeutics.

Study Design:
We will capture neuronal exosomes from the serum of people at risk of developing Parkinson’s using tools developed in our lab and measure their alpha-synuclein content. Our study will include individuals who have a specific sleep disorder or who carry genetic mutations that predispose them to PD. We will investigate whether the amount of exosomal alpha-synuclein found in these individuals correlates with a brain scan that reveals the death of dopamine-producing nerve cells. We will also study nerve cells generated from the individuals’ stem cells to determine whether the release of alpha-synuclein in exosomes can be used to monitor the effects of therapies that target the genetic mutations in PD. Lastly, we will further optimize the assay so that it can be scaled up for practical use in the clinic.  

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study is important because a predictive blood-based test is urgently needed to identify those individuals most likely to benefit from therapies that aim to stop or slow down Parkinson’s disease.

Next Steps for Development:
We will work with pharmaceutical companies and other stakeholders to develop a diagnostic kit and test individuals who have already entered clinical trials. 


  • George Tofaris, MBBChir, PhD, FRCP

    Oxford United Kingdom

  • Jason John Davis, PhD

    Oxford United Kingdom

  • Wolfgang H. Oertel, MD, PhD

    Marburg Germany

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