Study Rationale: Although Parkinson’s disease (PD) is known as a movement disorder, non-motor symptoms like anxiety can severely reduce individuals’ quality of life. Unfortunately, we know very little about what causes anxiety in PD. Research has begun to suggest that anxiety in PD may stem from pathology in an area of the brain called the amygdala. Given that the amygdala has long been known to play a role in anxiety, understanding this pathology and its effects on behavior will not only advance scientific knowledge, but also identify new ways to diagnose and treat people with PD.
Hypothesis: We predict that buildup of a PD-linked protein called alpha-synuclein in the amygdala will lead to anxiety development by altering the normal function of amygdala cells.
Study Design: We will use a newly developed preclinical model that overproduces a human form of alpha-synuclein, the protein that causes brain pathology in PD. We will monitor signs of anxiety and changes in movement for 2 to 4 months, after which will we assess brain pathology and function.
Impact on Diagnosis/Treatment of Parkinson’s disease: Successful completion of this work will fill a significant gap in the research field by identifying a way that human PD pathology drives the development of anxiety.
Next Steps for Development: Recent work has suggested that early symptoms like anxiety, when paired with biomarkers like alpha-synuclein, may be a very strong predictor of future PD diagnosis. This project will be important for improving early diagnosis and developing preventative and disease-altering therapies.