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Funded Studies

Non-dopaminergic Systems in the Evolution of LRRK2 Parkinsonism

Researchers have previously demonstrated that the pattern and evolution of progressive changes in the dopamine system in Parkinson’s disease (PD) associated with LRRK2 mutations are very similar to what is seen in non-inherited PD. We believe this will also be true for changes in other brain systems that may be involved even earlier than dopamine. Studying people with LRRK2 mutations will provide a unique opportunity to assess the natural history of PD even before it becomes clinically manifest.

Project Description:
We will use positron emission tomography (PET) to assess the function of other chemical systems in the brain, specifically serotonin and acetylcholine, among LRRK2-PD patients, non-inherited PD patients and healthy controls. These chemicals are produced by brain cells that may become involved earlier than dopamine. We will also assess the relationship between changes in these systems and loss of dopamine function, how different brain regions are interconnected (using functional MRI) and what relationship these changes have to the future development of motor and non-motor complications of PD.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
It has been suggested that while the main features of Parkinson’s are due to loss of dopamine in the brain, the disease may start in other brain regions many years before dopamine becomes involved. Involvement of these other regions may contribute to the development of complications. By studying people with LRRK2-PD and non-inherited PD, we can (i) confirm that LRRK2 is a good model for studying the progression of PD and (ii) assess how these changes may predict future complications.

Anticipated Outcome:
We expect that (i) changes in serotonin and acetylcholine systems in the brain will be similar between LRRK2-PD and non-inherited PD; (ii) studying unaffected LRRK2 mutation carriers will allow better understanding of the progression of PD and (iii) early changes in these systems will identify who is at risk for future complications. 


  • Vesna Sossi, PhD

    Vancouver BC Canada

  • A. Jon Stoessl, CM/MD/FRCPC/FCAHS

    Vancouver BC Canada

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