Study Rationale:
Brain inflammation, regulated by cells called microglia and astrocytes, has been shown to play a role in the initiation and progression of Parkinson’s disease. However, the role of astrocyte cells in the earliest disease stages (i.e., before the onset of movement symptoms) and how astrocytes could contribute to disease progression is not fully understood.
Hypothesis:
Changes in astrocytes could play a role in disease onset and could contribute to the progression of Parkinson’s disease.
Study Design:
We will use a technology called positron emission tomography (PET) that enables us to measure the activation of astrocytes in living patients using a novel radiotracer called [11C]BU99008. In this longitudinal study, the level of astrocyte activation will be compared across groups of (i) people with Parkinson’s-linked genetic mutations who have not yet shown movement symptoms, (ii) people with Parkinson’s from an unknown cause and (iii) control individuals at two time points (baseline and 12-month follow-up). This will allow us to investigate changes in astrocyte activation over time and the role of astrocytes in disease progression.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study could help to validate changes in astrocyte levels, measured in living patients with [11C]BU99008 PET, as a biomarker for disease onset and to monitor disease progression from premotor stages of Parkinson’s. Furthermore, our findings could open opportunities for the development of novel therapeutic interventions targeting astrocytes.