Funded Studies
Study Rationale: Cellular structures called mitochondria are functionally impaired in Parkinson’s disease (PD). How environmental toxins or lifestyle factors influence mitochondrial function and impaired clearance of damaged mitochondria in PD remain underexplored.
Hypothesis: Our overall hypothesis is that mitochondrial genes, lifestyle and environmental factors jointly influence age at onset (AAO) of both LRRK2-related and spontaneous, idiopathic PD.
Study Design: We will use large available genetic datasets to investigate whether AAO is influenced by: mitochondrial polygenic risk score (MRS) or common variants in mitochondrial DNA, cumulative rare variants in mitochondria-related genes or interactions between environmental factors — such as tobacco smoke, caffeine, pesticides or aspirin — and mitochondrial genetics or LRRK2 mutation. Finally, we will longitudinally assess how MRS and environmental factors influence PD motor and non-motor features.
Impact on Diagnosis/Treatment of Parkinson’s disease: This proposal will provide biological insight on mitochondrial pathways using genetic data and the influence of environmental effects such as inflammation and pesticides on PD. Identification of new mitochondrial-related genes that interact with lifestyle factors to influence AAO will provide new targets for PD treatment.
Next Steps for Development: We will identify new mitochondrial-related genes implicated in AAO that can help improve patient counseling and will improve our molecular understanding of PD-related mitochondrial pathways. Our next step could be exploring how these mitochondrial-related genetic variants and environmental factors influence mitochondrial biomarkers in brain, blood or CSF.